Genomically stabilized pluripotent stem cell populations and manufacture and use thereof

Abstract

The present disclosure provides genomically stabilized pluripotent stem cell (PSC) populations with reduced tumorigenic potential and methods of their production, maintenance, and use, e.g., in the production of differentiated cells for cell-based therapies. The disclosure further provides methods of identifying genomically stabilized PSCs, useful, e.g., in the processes of cell banking and manufacturing of cell therapies.

Description

GENOMICALLY STABILIZED PLURIPOTENT STEM CELL POPULATIONS AND MANUFACTURE AND USE THEREOF 1. CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the priority benefit of U.S. provisional application no.63 / 659,958, filed June 14, 2024, the contents of which are incorporated herein in their entireties by reference thereto. 2. SEQUENCE LISTING

[0002] The instant application contains a Sequence Listing which has been submitted electronically in XML format and is hereby incorporated by reference in its entirety. Said XML Sequence Listing, created on June 9, 2025, is named BRT-005WO_SL.xml and is 110,179 bytes in size. 3. BACKGROUND

[0003] Pluripotent stem cells (PSCs), such as induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs), are useful as precursors of differentiated cells for use in cell therapy.

[0004] For use in research and medicine, PSCs are preserved as collections of stem cells from a single genetic source referred to as “cell banks”.

[0005] During the process of PSC expansion in culture, e.g., to form cells banks or differentiate PSCs towards cell types with therapeutic potential, PSCs can acquire mutations that might increase the tumorigenic potential of a cell therapy. Such mutations can occur in the BCL6 Corepressor (“BCOR”) and retinoic acid receptor alpha (RARA) genes. BCOR is a tumor suppressor gene in which loss-of-function mutations, for example mutations that introduce a premature stop codon, are considered oncogenic and may impact the likelihood of developing certain cancers. RARA is a transcription factor that is associated with cell differentiation of white blood cells and in which mutations are associated with some cancers. Therefore, for the safety and efficacy of stem cell-based therapies it would be advantageous to select and use PSCs with a lower tumorigenic potential, such as PSCs with a lower BCOR and / or RARA mutational burden. 4. SUMMARY

[0006] The present disclosure relates to populations of genomically stabilized pluripotent stem cells (PSCs) and PSC cell lines, and methods of generating, maintaining, and using populations of PSCs and PSC cell lines, with a lower incidence of markers of genetic instability / markers of tumorigenic potential, such as BCOR and / or RARA mutations. Such PSCs and PSC cell lines are referred to herein as “genomically stabilized” for convenience.

[0007] Without being bound by theory, the inventors believe that lowering the incidence of markers of genetic instability / markers of tumorigenic potential in a cell population, e.g., lowering BCOR and / or RARA mutational burden, in a PSC population, reduces tumorigenic potential as compared to populations of PSCs that are not genomically stabilized. Genomically stabilized populations of PSCs are described in Section 6.2 and numbered embodiments 1 to 166 and the methods of producing genomically stabilized populations of PSCs are described in Section 6.3 and numbered embodiments 167 to 583.

[0008] The culture conditions under which populations of PSCs (referred to herein as PSC cell populations or PSC populations) are expanded from an ancestral cell or population of ancestral cells can impact whether or not tumorigenic genetic variants emerge and / or are selected for or against, and therefore, whether or not a genomically stabilized PSC population is produced, during expansion culture. The disclosure provides methods of creating PSC cell populations, e.g., for differentiation into cells that are formulated for therapeutic use, that promote genomic stability of the expanded cell populations. Typically, ancestor cells and their progeny are expanded with cell culture media that support PSC maintenance and expansion and in the presence of a laminin moiety. Exemplary cell culture containers and substrates suitable for expansion culture are described in Section 6.4 and numbered embodiments 130 to 132 and 584 to 590. Exemplary culture media are described in Section 6.5. Exemplary laminin moieties are described in Section 6.6 and numbered embodiments 108 to 129. Ancestral cells are described in Section 6.7 and numbered embodiment 257.

[0009] In certain aspects, the present disclosure provides methods of testing a PSC population, e.g., to determine whether it is a genomically stabilized population of PSCs, by testing for the prevalence of one or more markers of tumorigenic potential. The assays that relate to testing PSC populations is described in Section 6.8 and numbered embodiments 591 to 624.

[0010] In other aspects, the present disclosure provides methods of producing differentiated cell populations suitable for therapy. The use of genomically stabilized cell populations to produce cell therapy is described in Section 6.9 and numbered embodiments 625 to 642. 5. BRIEF DESCRIPTION OF THE FIGURES

[0011] FIG.1 is a schematic of an exemplary experimental strategy that was used to analyze BCOR mutations in pluripotent stem cell (PSC) populations under various culture conditions. As illustrated, two populations of Cell Line A, ones with and without the BCOR mutations (e.g., with and without two copies of BCOR mutated alleles, for instance, cell lines heterozygous for BCOR mutations and cell lines homozygous for BCOR mutations), are mixed at a 1:100 (1% mutant, 99% wildtype). The mixed cell populations are then subject to one of six different culture conditions as identified in the figure. Each culture condition is maintained for at least 15 passages prior to genetic analysis.

[0012] FIGS.2A – 2B shows exemplary experimental results for observed trajectories of variant allele frequencies (VAFs) for BCOR single nucleotide polymorphism 1 (SNP1) (FIG.2A) and BCOR single nucleotide polymorphism 2 (SNP2) (FIG.2B) in the mixed cell populations of Cell Line A. Each line reflects observations from a cell population that was cultured according to the identified culture condition from passage 0 (p0) to passage 15 (p15). The y-axis indicates the VAF, which was determined by digital droplet PCR (ddPCR). The x-axis identifies passage number.

[0013] FIG.3 shows exemplary experimental next-generation sequencing (NGS) results of VAFs for BCOR SNP1, BCOR SNP2, and RARA SNP in mixed cells of Cell Line A. The VAFs were detected from PSC cultures harvested at p15. The PSC cultures were generated using the culture conditions identified along the x-axis from p0 to p15. VAF is indicated along y axis. Data was generated using a NGS assay described herein. A1, A2, B2, B2, C1, C2, D1, D2, E1, E2, F1, and F2 refer to individual replicates for the indicated culture conditions.

[0014] FIGS.4A – 4C shows a schematic of an exemplary experimental plan for analyzing BCOR mutations in PSC lines under various culture conditions. The experimental plan is broken down into three parts: (A) Part 1; (B) Part 2; and (C) Part 3, which are described in the figure.

[0015] FIGS.5A – 5D show exemplary experimental results of a repeat experiment that was conducted to confirm the findings in FIGS 2A-2B and 3, displaying variant allele frequency (VAF) trajectories for BCOR SNP1 and SNP2 in mixed cells of Cell Line A when comparing culturing on LN521 versus Vitronectin (R&D- and CTS-grade) and with non-enzymatic Versene / EDTA clump versus single cell passaging (FIGS.5A and 5B), as well as when comparing non-enzymatic Versene / EDTA clump passaging with enzymatic TrypLE and Accutase single cell passaging on LN521 (FIGS.5C and 5D) from p0 to p8. Data was taken with a custom ddPCR assay, as described herein. VAF is indicated along the y-axis. Passage number is indicated along the x-axis.

[0016] FIGS.6A – 6B show exemplary experimental results of a rescue experiment aimed to determine whether PSCs with a higher starting variant allele frequency (VAF) of BCOR variants (>10% VAF) are rescued when cultured long-term (8 passages) on LN521 compared to vitronectin, displaying variant allele frequency (VAF) trajectories for BCOR SNP1 (FIG.6A) and BCOR SNP2 (FIG.6B) in mixed cells of Cell Line A when cultured on vitronectin versus LN521 from p0 to p8. Data was collected using a custom ddPCR assay described herein. VAF is indicated along the y-axis. Passage number is indicated along the x-axis.

[0017] FIG.7 shows exemplary experimental results of VAFs for BCOR SNP1 through SNP4 in Cell Line B at passage 8 (p8), when cultured on vitronectin versus LN521 from p0 to p8. VTN-1and VTN-2 correspond to replicates using vitronectin, LN521-1 and LN-521-2 correspond to replicates using LN521. The VAFs were measured using the NGS assay.

[0018] FIG.8 shows a schematic of an exemplary experimental plan for analyzing BCOR mutations in PSC lines under different culture conditions. In some embodiments, a LN521 coating at 1 µg is performed at room temperature for 2 hours and / or a LN521 coating at 0.5 µg is performed at 4°C for 3-4 days.

[0019] FIGS.9A – 9B show exemplary experimental results for VAF trajectories for BCOR SNP1 (FIG.9A), and BCOR SNP2 (FIG.9B) in mixed cells of Cell Line A when cultured on vitronectin versus LN511-E8 from p0 to p8. Data was collected using a custom ddPCR assay described herein.

[0020] FIG.10 shows exemplary experimental results of variant allele frequencies (VAFs) for BCOR SNP1, BCOR SNP2 and RARA SNP in mixed cells of Cell Line A as measured by next- generation sequencing. The VAFs were detected with PSC cultures harvested at p8. The PSC cultures were cultured using one of six different culture conditions (identified along x axis) from p0 to p8. VAF is indicated along y axis. Data was generated using an NGS assay described herein. The notation (p.?) means the consequence of a variant in a splice acceptor / donor site on protein sequence is unknown.

[0021] FIG.11 illustrates an exemplary process for producing therapeutic cells. Steps 1-9 illustrate producing therapeutic cells from a starting cell population that is reprogrammed into iPSCs. An iPSC colony can be considered an ancestral cell, and each cycle of expansion, cell banking and / or cell reactivation, when carried out under appropriate conditions (e.g., as set forth in Section 6.3), can result in the production of a genomically stabilized population of iPSCs as described in Section 6.2. A similar workflow can be used to produce therapeutic cells from a starting cell population of other types of PSCs, e.g., ESCs, beginning at step 4 of the illustrated process.

[0022] FIGS.12A-12B show the relationship between cell seeding density and confluency. FIG.12A shows microscopy images of cells seeded at various seeding densities on passage day (Day 4) before dissociation. FIG.12B shows the percentage confluency of each culture.

[0023] FIGS.13A-13C show the differences in BCOR SNP1 variant allele frequency percentage ( SNP1 %VAF) in PSC populations with low (FIG.13A), standard (std) (FIG.13B), or high (FIG.13C) percentage confluency at Day after EDTA or TrypLE harvesting of the cells.

[0024] FIG.14 shows differences in accumulation of BCOR SNP1 %VAF over passages in iPSC populations harvested using aggregate (clump passaging) or single cell dissociation methods in the presence of Y-27632.

[0025] FIGS.15A-15D show the effect of harvesting method on dissociation efficiency and BCOR SNP1 %VAF of iPSCs seeded on vessels coated with LN521 (FIGS.15A and 15B) or LN511-E8 (FIGS.15C and 15D).

[0026] FIG 16 Schematic of the experimental design of studies described in Example 6. Two clonal populations of PSCs with a known BCOR SNP1 VAF of either 50% (100% of the population due to heterozygosity) or 0% (WT) were thawed and mixed to generate a new population of cells with a SNP1 VAF of 25%. These cells were plated in duplicate flasks coated with either LN521 or LN511-E8 alongside the 0% SNP1 cells. Following a 4-day growth period, replicate flasks were passaged independently into a new vessel, maintaining the same coating substrate as the previous vessel. A dual-dissociation approach was applied, whereby cells were initially dissociated with EDTA at room temperature and passaged into the new vessel and a cell pellet was retained for ddPCR analysis. Any remaining cells still adherent to the LN surface were removed with the enzymatic reagent Accutase and collected by centrifugation for ddPCR analysis. This was repeated for a total of 8 passages, with cells being cryopreserved and thawed after passage 4. EDTA dissociation time was consistent between all conditions, with the duration being determined by the length of time it took for the 0% SNP1 population to achieve 100% dissociation (7 min).

[0027] FIGS.17A-17B show the negative selection of BCOR SNP1 in a PSC population over eight passages and one cryopreservation event on either LN521 (FIG.16A) or LN511- E8 (FIG.16B) coated vessels using EDTA dissociation at room temperature with a fixed incubation time of seven minutes. Individual vessels were subsequently treated with Accutase at each passage to remove EDTA resistant cells, which exhibit a higher SNP1 VAF.

[0028] FIG 18 depicts the relationship between the initial SNP1 VAF of a PSC population (0% or 26.9%) and the percentage of total cells in the vessel that can be successfully dissociated with EDTA at room temperature after 4 days in culture on LN521 and LN511-E8 coated vessels. Cells unable to be dissociated with EDTA were recovered with Accutase. The SNP1 VAF of each respective cell population on day 4 harvest was analyzed by ddPCR.

[0029] FIGS.19A-19F show accumulation of EP300 or BCORdel1072 mutants for different cell protection supplement treatments and passaging frequencies. FIG.19A shows changes in percentage of EP300 VAF over time in PSCs treated with Y-27632 or CEPT cocktail and passaged at 48 hours. FIG.19B shows changes in percentage of EP300 VAF over time in iPSCs treated with Y-27632 or CEPT cocktail and passaged at 72 hours. FIG.19C shows changes in percentage of EP300 VAF over time in PSCs treated with Y-27632 or CEPT cocktail and passaged at 96 hours. FIG.19D shows changes in percentage of BCORdel1072 VAF over time in PSCs treated with Y-27632 or CEPT cocktail and passaged at 48 hours. FIG.19E shows changes in percentage of BCORdel172 VAF over time in PSCs treated with Y-27632 or CEPT cocktail and passaged at 72 hours. FIG.19F shows changes in percentage ofBCORdel1072 VAF over time in PSCs treated with Y-27632 or CEPT cocktail and passaged at 96 hours.

[0030] FIGS.20A-20B show exemplary results from two assessments in which a PSC line with a low starting VAF of BCOR SNP1 and BCOR SNP2 was cultured for 5 passages on laminin 521 substrate and clump passaged using EDTA with Y-27632 supplementation for 24 hours after passage (Parental Culture). On the 5th passage this cell population was either maintained with this same culture protocol (+Y-27632) or switched to a culture protocol with CEPT supplementation rather than Y-27632 for 24 hours after passage (+CEPT) for an additional 4 passages. Samples were collected at each passage and a custom ddPCR assay was used to measure the VAF of BCOR SNP1 (FIG.20A) and the VAF of BCOR SNP2 (FIG.20B) in each sample. Passaging with the addition of CEPT resulted in a lower frequency of both BCOR SNPs throughout the culture duration as compared to Y-27632.

[0031] FIGS.21A-21B show exemplary results from two assessments in which a PSC line containing both BCOR SNP1 and BCOR SNP2 (Parental Culture) was harvested using Accutase and seeded at a “clonal” density of 25 cells / cm2 either in media containing Y-27632 (Clonal +Y-27632) or media containing CEPT (Clonal +CEPT) for 48 hours. Following seeding, cells were allowed to grow into single cell colonies for 7 days. A pooled sample of each condition was collected after 7 days and a custom ddPCR assay was used to measure the VAF of BCOR SNP1 (FIG.21A) and the VAF of BCOR SNP2 (FIG.21B) in each sample. Clonal density seeding with the addition of CEPT resulted in a lower final frequency of both BCOR SNPs as compared to Y-27632.

[0032] FIGS.22A-22E show experimental process and results of assessments in which the ability of laminin 511-E8 fragment to reduce the prevalence of 20q11.21 band duplication was evaluated. FIG.22A shows the setup of the experimental process. FIG.22B shows changes in 20q mean copy number variants (20q mean CNV) in cells seeded on LN511-E8 fragment or LN521 coated vessels between P0 and P8. FIG.22C shows changes in mean CNV across repeats for cells seeded on LN521-coated vessels from P0 to P12. FIG.22D shows changes in 20q mean copy number variants (20q mean CNV) in cells seeded on LN511-E8 fragment or LN521 coated vessels between P0 and P12. FIG.22E shows changes in mean CNV across repeats for cells seeded on LN521-coated vessels from P4 to P12.

[0033] FIGS.23A-23G show the effect of different media on viability and other cell culture properties. FIG.23A shows the viability percentages of cultures subjected to different culture media at P4. FIG.23B shows the aggregate percentages of cultures subjected to different culture media at P4 harvest. FIG.23C shows changes in confluence of cultures subjected to different culture media between the start of the assessment and P5. FIG.23D shows viability percentages of cultures subjected to different culture media after thawing of P4. FIG.23E shows the recovery percentages of cultures subjected to different culture media after thawing ofP4. FIG.23F shows viability percentages of cultures subjected to different culture media at P5 harvest. FIG.23G shows the aggregate percentages of cultures subjected to different culture media at P5 harvest.

[0034] FIGS.24A-24E show culture media-associated changes in BCOR SNP1 and SNP2 VAFs and changes in 20q copy numbers. FIG.24A shows the starting value and differences in BCOR SNP1 VAF across different media conditions at P4. FIG.24B shows he starting value and differences in BCOR SNP2 VAF across different media conditions at P4. FIG.24C shows differences in BCOR SNP1 VAF across different media conditions at P5. FIG.24D shows differences in BCOR SNP2 VAF across different media conditions at P5. FIG.24E shows he starting value and differences in 20q copy numbers across different media conditions at P5. 6. DETAILED DESCRIPTION 6.1. Definitions

[0035] Unless otherwise defined herein, scientific and technical terms used in connection with the present disclosure shall have the meanings that are commonly understood by those of ordinary skill in the art. Exemplary methods and materials are described below, although methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present disclosure. In case of conflict, the present specification, including definitions, will control. Generally, nomenclature used in connection with, and techniques of, cell and tissue culture, molecular biology, immunology, microbiology, genetics, analytical chemistry, synthetic organic chemistry, medicinal and pharmaceutical chemistry, and protein and nucleic acid chemistry and hybridization described herein are those well-known and commonly used in the art. Enzymatic reactions and purification techniques are performed according to manufacturer’s specifications, as commonly accomplished in the art or as described herein. Further, unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular. Throughout this specification and embodiments, the words “have” and “comprise,” or variations such as “has,” “having,” “comprises,” or “comprising,” will be understood to imply the inclusion of a stated integer or group of integers but not the exclusion of any other integer or group of integers. All publications and other references mentioned herein are incorporated by reference in their entirety. Although a number of documents are cited herein, this citation does not constitute an admission that any of these documents forms part of the common general knowledge in the art.

[0036] The practice of some methods disclosed herein employ, unless otherwise indicated, conventional techniques of immunology, biochemistry, chemistry, molecular biology, microbiology, cell biology, genomics and recombinant DNA, which are within the skill of the art. See for example Sambrook and Green, Molecular Cloning: A Laboratory Manual, 4th Edition (2012); the series Current Protocols in Molecular Biology (F. M. Ausubel, et al. eds.); the series Methods In Enzymology (Academic Press, Inc.), PCR 2: A Practical Approach (M. J.MacPherson, B.D. Hames and G.R. Taylor eds. (1995)), Harlow and Lane, eds. (1988) Antibodies, A Laboratory Manual, and Culture of Animal Cells: A Manual of Basic Technique and Specialized Applications, 6th Edition (R.I. Freshney, ed. (2010)); Barbare Detrick, Robert Hamilton, John L Schmitz, Manual of Molecular and Clinical Lab Immunology (2016).

[0037] A, An, The: As used herein, the articles “a,” “an,” and “the” are used herein to refer to one or to more than one (e.g., to at least one) of the grammatical object of the article. By way of example, “an element” means one element or more than one element.

[0038] The use of the alternative (e.g., “or”) should be understood to mean either one, both, or any combination thereof of the alternatives.

[0039] BCOR: As used herein, the term “BCOR” is used to refer to BCL6 co-repressor. BCOR is a transcriptional repressor that is associated with normal germinal center formation in B cells. BCOR is a chromatin regulatory protein that functions in a variety of non-canonical epigenetic repressive complexes and binds the transcriptional repressor BCL6. Depletion of BCOR is associated with a loss of Polycomb protein binding at target genes, which is important for maintaining repressed chromatin. An exemplary BCOR gene is available as Gene ID: 54880 (e.g., available at the website www.ncbi.nlm.nih.gov / gene / 54880).

[0040] The BCOR gene is located on the X chromosome. Male cells have only one copy of the X chromosome, and therefore, each male cell expresses a single BCOR allele. Thus, when measuring variant allele frequency (VAF) that correspond to a given BCOR single nucleotide polymorphism (SNP) via PCR, the percentage of cells with a BCOR SNP in male cell lines reflects the genotype frequency for that SNP, for which the maximum VAF for BCOR SNPs can reach 100%. In contrast, female cells have two copies of the X chromosome, and thus each female cell has two BCOR alleles, which may be the same or different. One copy of the X chromosome is inactivated in female cells as a result of X-chromosome inactivation (XCI), a form of dosage compensation in mammalian female cells to balance X-linked gene expression levels of the two sexes. See Sun et al., 2022, Genet Res (Camb).2022:1391807. X- chromosomes inactivation is stably inherited by all daughter cells through mitosis (i.e., all daughter cells have the same X chromosome inactivated as their mother cell). Thus, in female cells, one copy of the BCOR gene is active and the other is inactivated due to XCI. Given that only the active X chromosome of a female cell is available to accumulate BCOR mutations, the maximum variant allele frequencies (VAFs) for BCOR SNPs in a population of female cells in a starting cell without the BCOR SNPs is 50% at the genotype level. Therefore, the maximum VAF% for a given BCOR SNP in a population of female PSCs is 50%.

[0041] Cell Bank: The term “cell bank” refers to a repository of cells in storage. Typically, the cells are preserved, e.g., in a cryopreservation solution. The cells in a cell bank may be cells of any organism. In some embodiments, the cells of a cell bank are human cells. In otherembodiments, the cells are derived from mammals other than humans, such as rats, mice, monkeys, cats, sheep, etc.; they may also be derived from birds, such as chickens. Cells in a cell bank can be kept for years, decades or longer.

[0042] Cell Culture Container, Culture Container, Cell Culture Vessel: As used herein, the terms “cell culture container,” “culture container” and “cell culture vessel” refer to any container or receptacle suitable for or specifically designed to contain cell cultures and are preferably suitable to grow and expand cells in or on a medium. Typical cell culture containers are flasks, plates, tubes, multi-well plates, bioreactors and the like. Culture containers can be reusable or disposable. Typically, culture containers are made of plastic, typically optically transparent plastic, such as polystyrene or polycarbonate. Glass cell culture containers can also be used. In some embodiments, disposable cell culture containers are used to reduce the risk of contamination. In some embodiments, cell culture containers are made of polystyrene.

[0043] Cell culture plates refer to multi-well containers, typically rectangular structures comprising a plurality (such as, e.g., 4, 6, 8,12, 24, 48, 96, 384 or 1536) of shallow wells that are often round. Cell culture dishes may refer to single-well shallow containers such as, e.g., Petri dishes, which are circular shallow dishes, and are typically lidded. Cell culture dishes may also refer to rectangular cell culture dishes. Cell culture tubes refer to cylindrical or conical containers which can have a round or flat bottom surface, and are typically lidded. Cell culture flasks refer to containers that have a wider vessel “body” and one or more narrower tubular sections called necks that connect the body to an opening, which is typically lidded. Commonly used cell culture flasks have a parallelepiped shape with a flat and typically rectangular bottom surface.

[0044] Cell Reactivation, Reactivation: As used herein, the terms “cell reactivation” and “reactivation” refer to the process of reactivation of dormant cells, e.g., cryopreserved cells in a cell bank. For example, a cryopreservation container containing cryopreserved cells is collected from a cell bank and then contacted with a solid, liquid or gaseous medium (e.g., water, culture medium) having a temperature higher than the cryopreservation temperature, e.g., by using a water bath, an incubator, or the like. The temperature of the medium is typically 4°C-50°C, preferably 30°C-40°C, more preferably 36°C-38°C. The thawing time is typically within 2 minutes, and in some embodiments about 20 seconds, whereby a decrease in the survival rate of the cell can be drastically suppressed. The thawing time can be adjusted by, for example, changing the thawing means, temperature of immersion medium, volume or composition of the culture medium or cryoprotective solution during freezing, and the like.

[0045] The cells can be washed by a known method. For example, the method includes, but is not limited to, suspending the cells in a cell washing (e.g., culture medium or biological buffer etc. containing serum, serum components (serum albumin and the like)), centrifuging same, discarding the supernatant, and collecting the precipitated cells. In the process of washing thecells, the cycle of suspending, centrifugation, and recovery may be performed once or plural times (e.g., 2, 3, 4, 5 or more). In one embodiment, the process of washing the cells is performed immediately after the process of thawing banked cells. Examples of commercially available cell washing solutions that can be used include CELLOTION (Japan ZENYAKU KOGYO) and the like.

[0046] In some embodiments, the thawed cells are pre-cultured, e.g., prior to expansion. The preculture and maintenance culture can be performed for an appropriate culture period according to the purpose. The culture period is preferably not less than 1 day (e.g., 5, 6, 7 days) and not more than 10 days (e.g., 7, 8, 9, 10 days). The culture temperature is not particularly limited and in some embodiment ranges between 30°C and 40°C, and is preferably 37°C. Culture can be performed in the presence of CO2-containing air, e.g., at a CO2concentration of about 2%-5%.

[0047] Cryopreservation: The freezing of cells is ordinarily destructive, such as due to ice crystal formation, osmotic dehydration and increased intracellular solute concentration during cooling and / or freezing. These injurious effects can be circumvented by (a) use of a cryoprotective agent, (b) control of the freezing rate, and (c) storage at a temperature sufficiently low to minimize degradative reactions. Cells can be stored using conventional equipment and methods, which include, but are not limited to, placing the container containing the cells in a freezer (e.g., ultra-low temperature freezer), and bringing the cells into contact with a low temperature medium (e.g., liquid nitrogen, etc.) and preserving them in a freezer or cryopreservation system).

[0048] In some embodiments, a program cooling method may be used. Cryopreserving cells with a program cooling method can be achieved by providing a freezing means set to a desired temperature in contact with a container containing cells directly or after accommodating the container in a freezing treatment container, e.g., a freezing treatment container such as a BICELLTM, Mr. Frosty or CoolCell container. The freezing temperature is typically not more than 0° C, preferably not more than −20°C, more preferably not more than −40°C, and in some embodiments not more than −80°C. The freezing treatment container may have a function of controlling the rate of temperature decrease inside the container to a predetermined speed. For instance, the cooling rate can be achieved by using a freezer whose cooling rate can be controlled by setting a program, such as a program freezer (e.g., KryoMed (Thermo Fisher), PDF-2000G (Strex), KRYO-560-16 (Asahi Life Science)). The cooling rate in the freezing operation is typically a cooling rate of 1-5 hours, for example 2-4 hours, particularly about 3 hours, from the start of cooling at 4°C to reach −80°C. A typical cooling program comprises a cooling rate of -1°C / min to -2°C / min; when the temperature reaches below -25°C, the cooling rate can be adjusted to -5°C / min to -10°C / min; when the temperature reaches -100°C, the cellcontainer can be quickly immersed in liquid nitrogen. Cells can be stored in liquid nitrogen for decades or longer.

[0049] The freezing operation can be performed using a culture medium in which colonies were immersed, a physiological buffer solution, or the like as a cryoprotective solution, and treating the solution by adding a cryoprotective agent, or replacing the culture medium with a cryoprotective solution containing a cryoprotective agent. When replacing the culture medium with a cryoprotective solution, the cryoprotective solution may be added after substantially removing all the culture medium, or the cryoprotective solution may be added while leaving a part of the culture medium. The cryoprotective solution may be commercially available and, for example, CryoStorTMCS10, and STEM-CELLBANKERTM(ZENOAQ) can be used.

[0050] The nonlimiting examples of cryoprotective agents include dimethyl sulfoxide (DMSO), ethylene glycol (EG), propylene glycol (PG), 1,2-propanediol (1,2-PD), 1,3-propanediol (1,3- PD), butyleneglycol (BG), isopreneglycol (IPG), dipropylene glycol (DPG), and glycerol. The cryoprotective agent may be used alone or two, three or more cryoprotective agents may be used in combination. Moreover, the cryoprotective agent may be used in combination with an extracellular cryoprotective agent. Nonlimiting examples of the extracellular cryoprotective agent include polyethylene glycol, carboxymethylcellulose sodium, polyvinylpyrrolidone, hydroxyethyl starch (HES), dextran, and albumin.

[0051] The concentration of the cryoprotective agent added to the culture medium, or the concentration of the cryoprotective agent in the cryoprotective solution, is typically 2%-20% (v / v), for example 5%-15% and in some embodiments 8%-13%, of the total culture medium or cryoprotective solution. The above-mentioned concentration ranges can be appropriately adjusted by the type of cryoprotective agent. For example, when DMSO is used as the cryoprotective agent, concentration of DMSO is typically 2%-20% (v / v), typically 2.5%-12.5%, for example 5%-10%, of the total culture medium or cryoprotective solution.

[0052] A cryopreservation container can be used. Specific examples of cryopreservation containers include but are not limited to aseptic vials (e.g., glass ampoule, polymer vial (AT- closed vial) etc.).

[0053] Cryopreservation Container: As used herein, the term “cryopreservation container” refers to any container or receptacle suitable for cryopreservation of cells, e.g., a sterile or aseptic vial or ampoule. In some embodiments, the vial or ampoule has a volume of 1 mL – 3 mL (e.g., 1.5 mL, 1.8 mL or 2 mL).

[0054] Differentiation: As used herein, the term “differentiation”, and its grammatical equivalents, refers to a process by which a stem cell or progenitor cell alters from one cell type to a more specialized cell type. Each specialized cell type in an organism can express a subset of all the genes that constitute the genome of the cell. Each cell type can be defined by itsparticular pattern of regulated gene expression. Cell differentiation can thus be described as a transition of a cell from one cell type to another cell type coincident with a switch from one pattern of gene expression to another.

[0055] EP300: As used herein, the term “EP300” refers to E1A binding protein p300. EP300 is a tumor suppressor and histone acetyltransferase and is inactivated in various cancer types. EP300 is also a transcriptional co-activator with histone acetyltransferase (HAT) activity that is homologous to the co-activator CREBBP. An exemplary EP300 gene is available as Gene ID: 2033 (e.g., available at the website www[dot]ncbi[dot]nlm[dot]nih[dot]gov / gene / 2033).

[0056] Expanded Pluripotent Intermediate Cell Bank: As used herein, the term “expanded pluripotent intermediate cell bank” or “epi bank” refers to an expanded isogenic cell population (e.g., an isogenic PSC population) that has been dispensed into storage containers (e.g., at least 10, at least 20 or at least 50 storage containers such as storage vials), the majority (or each) of which contain(s) a single cell, and stored, for example under cryopreservation conditions, e.g., for later use. In some embodiments, an epi bank is generated from a population of cells that has undergone three cryopreservation / thawing cycles, each followed by expansion in vitro. An epi bank can be generated by thawing and expanding cells from a working cell bank and then cryopreserving individual cells from the expanded population. In some embodiments, the expansion entails three or more rounds of passaging (e.g., clump passaging), e.g., three, four, five or more rounds of clump passaging.

[0057] Expanding, Expansion: The methods of the present disclosure may include a step of culturing cells, e.g., from a cell bank (such as, but not limited to, a seed cell bank, master cell bank, or a working cell bank) in order to expand a population, e.g., prior to differentiation, selection and / or banking. As used herein, the terms “expanding” and “expansion” refer to culturing cells under proliferation conditions to increase the cell number. A cell culture undergoing expansion might be subject to one or more rounds of passaging, e.g., to maintain suitable conditions for expansion and / or for the health of dividing cells.

[0058] Expansion Phase: As used herein, the term “expansion phase” refers to a period of culturing cells between passages.

[0059] Expansion Media: As used herein, the term “expansion media” refers to cell culture media suitable for expanding cells, e.g., PSCs.

[0060] Genomically Stabilized Cell: As used herein, the term “genomically stabilized cell” refers to a cell that (a) is the progeny of at least 3 cell passages (e.g., 3, 4, 5 or more) cell passages in culture from one or more cells of an in vitro cell population, e.g., an in vitro clonal cell population, referred to herein as an “ancestral” cell population and cells within it “ancestral” cells and / or (b) lacks a marker of genetic instability / tumorigenic potential, such as BCOR SNP1 (c.572G>A), BCOR SNP2 (c.4819+1G>A), RARA SNP (c.352G>T), or any combinationof two or all three SNPs of BCOR SNP1, BCOR SNP2, and RARA SNP. In some embodiments, a genomically stabilized cell lacks chromosomal rearrangements. In some embodiments, the genomically stabilized cell is a PSC (such as, but not limited to, an iPSC or an ESC). In some embodiments, the genomically stabilized cell is from a cell bank (e.g., a seed bank, a master cell bank, or a working cell bank) or from a cell culture. In some embodiments, the ancestral cell population is an iPSC colony. In some embodiments, the genomically stabilized cell is the product of at least one, at least two or at least three cryopreservation-reactivation cycles (e.g., one, two, three or four cryopreservation-reactivation cycles). In some embodiments, the genomically stabilized cell is the progeny of at least 5, at least 6, at least 7, at least 8, at least 9 or at least 10 cell divisions in culture from an ancestral cell population.

[0061] Genomically Stabilized Cell Population, Genomically Stabilized Population: As used herein, the terms “genomically stabilized cell population” and “genomically stabilized population” refers to a cell population in which at least 90% of the cells are genomically stabilized. In various embodiments, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.9% or at least 99.95% of the cells in a genomically stabilized cell population are genomically stabilized. In some embodiments, a genomically stabilized population does not contain a detectable level of one or more markers of genetic instability / tumorigenic potential, e.g., a BCOR and / or RARA mutation. In some embodiments, a genomically stabilized cell population is cryopreserved in a vial (e.g., at a concentration of 0.5-10 x 106cells / mL) and / or comprises at least 0.5x106cells (e.g., 0.5-10 x 106cells). In some embodiments, the genomically stabilized cell population is a population comprising or consisting of PSCs (such as, but not limited to, iPSCs or ESCs) or cells undergoing differentiation therefrom. Unless the context dictates otherwise, the terms “genomically stabilized cell population” and “genomically stabilized population” refer not to a fixed population of cells but also parental and progeny cells in which the at least 90% of the cells, e.g., at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.9% or at least 99.95% of the cells, are genomically stabilized. The terms “genomically stabilized cell population” and “genomically stabilized population” are not intended to convey a mechanism of action, and encompass cell populations with a low incidence of genetic instability markers / tumorigenic potential markers resulting from any mechanism, including but not limited to culture conditions that suppress emergence of and / or select against cells having such markers.

[0062] Isogenic: As used herein, the term “isogenic” refers to cells having the same or closely similar genotypes. Cells that are isogenic share the same genetic background but may have a small number of genetic differences (e.g., 2, 3, 4, 5, 10 or 20 genetic differences), for example differences that spontaneously arise during cell culture). The term “isogenic” encompasses the term “monogenic,” which refers to cells of the same genotype.

[0063] Laminin: As used herein, the term “laminin”, and its grammatical equivalents, refers to a family of glycoproteins associated with the cell basement membrane. These proteins are generally trimeric, consisting of alpha, beta, and gamma chains, which assemble into a cross- shaped molecule capable of binding to cell receptors, other matrix components, and growth factors.

[0064] Laminin Moiety: As used herein, the term “laminin moiety” refers to a laminin peptide, polypeptide or protein that supports adhesion of PSCs to a substrate, e.g., a cell culture container. The term “laminin moiety” encompasses the complete spectrum of chemical entities that have at least an amino acid polymer component with an amino acid sequence similar to, homologous to, orthologous to, or identical to a naturally occurring laminin molecule, including, by way of illustration, inter alia, a higher order molecular complex containing multiple proteins or polypeptide chains (e.g., e.g., a ternary complex), a multi-subunit protein with two or more peptide or polypeptide chains, a polypeptide chain, a chimeric polypeptide chain (e.g., a polypeptide with laminin sequences and non-laminin sequences, such as another extracellular matrix protein sequence or a molecular tag, etc.), a chemically derivatized polypeptide or higher order protein having laminin sequences and an active moiety, such as to facilitate binding to a substrate (e.g., tissue culture plate plastic), or tracking (e.g., I125), a proteoglycan containing a laminin sequence, a peptide or oligopeptide containing a laminin sequence, and the like. In some embodiments, the laminin moiety comprises a full-length laminin. In some embodiments, the laminin moiety comprises LN521. In some embodiments, the laminin moiety comprises one or more laminin fragments. In some embodiments, the laminin moiety comprises a fragment of a laminin protein. In some embodiments, the laminin moiety comprises LN-511-E8. Exemplary laminin moieties and sources are disclosed in Section 6.6. The term “laminin moiety” encompasses combination of individual laminin peptides, polypeptides and / or proteins, including but not limited to those described in Section 6.6.

[0065] Master Cell Bank: As used herein, the term “master cell bank” or “MCB” refers to an expanded isogenic cell population (e.g., an isogenic PSC population) that has been dispensed into storage containers (e.g., at least 10, at least 20 or at least 50 storage containers such as storage vials) and stored, for example under cryopreservation conditions, e.g., for later use. In some embodiments, a master cell bank is generated from a population of cells that has undergone one cryopreservation / thawing cycle followed by expansion in vitro. A master cell bank can be generated by thawing and expanding cells from a seed cell bank and then cryopreserving cells from the expanded population. In some embodiments, the expansion entails three or more rounds of passaging (e.g., clump passaging), e.g., three, four, five or more rounds of clump passaging.

[0066] Passaging, Passage: As used herein in the context of a cell culture, the terms “passaging” and “passage” shall refer to the transfer of all or a portion cells, e.g., from aprevious cell culture, into a new cell culture. The transfer can be done into a new cell culture container, such as a dish, bottle or flask, having fresh cell culture medium that allows for further culturing and / or expansion of the cells. One type of passaging used in the methods of the disclosure is “clump passaging,” which involves transferring adherent cells as clumps or aggregates. In some embodiments, for generation and / or maintenance of genomically stabilized cell populations, clump passaging is performed during most or all phases of cell expansion. In some embodiments, clump passaging utilizes a chelator such as EDTA rather than proteases to detach adherent cells from their cell culture container. A suitable method of clump passaging comprises contacting a population of adherent cells with a chelator such as EDTA, e.g., at room temperature (19-23°C) for 5-25 minutes (and in some embodiments 7-20 minutes, 8-11 minutes, 8-15 minutes, or 8-20 minutes) followed by gentle flushing and trituration to collect cells. Another suitable method of clump passaging comprises contacting a population of adherent cells with a chelator such as EDTA, e.g., at room temperature (19-23°C) for 25-50 minutes (and in some embodiments 30-45 minutes, 25-35 minutes, 30-40 minutes, 35-45 minutes or 40-50 minutes) followed by gentle flushing and trituration to collect cells. Another suitable method of clump passaging comprises contacting a population of adherent cells with a chelator such as EDTA, e.g., at room temperature (19-23°C) for no more than 7 minutes (e.g., 7 minutes, 6 minutes, or 5 minutes) followed by gentle flushing and trituration to collect cells. Clump passaging may also include a step of removing non-adherent cells together with old cell culture medium, e.g., prior to contacting them with a chelator. New cell culture medium can be added to the remaining adherent cells prior to transferring to a new cell culture container. The cell culture medium used for passaging can comprise one or more supplements, e.g., cell protection supplements. Exemplary cell protection supplements include ROCK inhibitors, such as Y-27632 (herein also referred to as ROCKi), Thiazovivin and Chroman 1. Additional cell protection supplements are CloneR® and CloneR2®. In some embodiments, cell protection supplement comprises a cell protection supplement cocktail containing a ROCK inhibitor and one or more additional cell protection supplements, such as a caspase inhibitor (e.g., Emricasan), one or more polyamines (e.g., a mixture of Putrescine, Spermine, and Spermidine), and / or an ISR inhibitor (e.g., trans-ISRIB). In some embodiments, the cell protection supplement cocktail comprises CEPT cocktail, which comprises Chroman1, Emricasan, polyamines, and trans-ISRIB. CEPT cocktails are commercially available, for example Thermo Fisher catalog number A56799. In some embodiments, cell protection supplement comprises a cell protection supplement cocktail containing a ROCK inhibitor and one or more additional cell protection supplements, such as an antioxidant and / or molecules that scavenge free radicals. In some embodiments, the cell protection supplement cocktail comprises Revitacell™, which comprises a ROCK inhibitor and molecules with antioxidant and free radical scavenger properties.

[0067] Pluripotent Stem Cell, PSC: As used herein, the term “pluripotent stem cell”, and its grammatical equivalents, refers to a stem cell that has the capacity for self-renewal and the potential to differentiate into a more specified cell type. Examples of pluripotent stem cells include embryonic stem cells, fetal stem cells, embryonic germ cells, induced pluripotent stem cells, and the like. A stem cell established by cultivating an early embryo generated by transplantation of the nucleus of a somatic cell is also a pluripotent stem cell. The pluripotent stem cell may be an animal cell, a vertebrate cell, a mammalian cell, a primate cell, or human cell.

[0068] Seed Cell Bank, Seed Bank: As used herein, the term “seed cell bank” or “SCB” (or sometimes simply “seed bank”) refers to an expanded isogenic cell population (e.g., an isogenic PSC population) that has been dispensed into storage containers (e.g., at least 10, at least 20 or at least 50 storage containers such as storage vials) and stored, for example under cryopreservation conditions, e.g., for later use. In some embodiments, a seed cell bank is generated from a population of cells that has not undergone any cryopreservation / thawing cycles. In some embodiments, a PSC seed cell bank is the first PSC bank generated after reprogramming cells (e.g., somatic cells) into iPSCs.

[0069] Substrate: As used herein throughout the disclosure, in the practice of the disclosure or any and all aspects of the disclosure, the term “substrate” is broadly construed to include any two-dimensional surface of any material. That two-dimensional surface can have any format, such as, e.g., cell culture container such as a tissue culture plate surface, a flask surface, tissue culture wells, or a bioreactor surface. A useful substrate may contain, include, or consist of glass, plastic, biological, cellular, acellular, and the like material. For example, a cell culture container surface may be polystyrene. In some embodiments, “substrate” includes complex surfaces, such as a plastic, glass, or other stiff surface coated or functionalized with one or more molecules, materials, moieties, and / or functionalized or activated groups.

[0070] RARA: As used herein, the term “RARA” refers to retinoic acid receptor alpha. RARA is a transcription factor that is associated with cell differentiation of white blood cells. Mutations within RARA are associated with some cancers. An exemplary RARA gene is available as Gene ID: 5914 (e.g., available at the website www[dot]ncbi[dot]nlm[dot]nih[dot]gov / gene / 5914).

[0071] Reduce, Reduced, Reduction: As used herein, the terms “reduce”, “reduced”, “reduction”, and its grammatical equivalents, refer to any statistically significant reduction in an occurrence (e.g., occurrence or detection of a mutation). For example, in the context of the present disclosure, a reduction can refer to a reduction of about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% in the occurrences of a BCOR mutation as compared to a control.

[0072] Working Cell Bank: As used herein, the term “working cell bank” or “WCB” refers to an expanded isogenic cell population (e.g., an isogenic PSC population) that has been dispensed into storage containers (e.g., at least 10, at least 20 or at least 50 storage containers such as storage vials) and stored, for example under cryopreservation conditions, e.g., for later use. In some embodiments, a working cell bank is generated from a population of cells that has undergone two cryopreservation / thawing cycles, each followed by expansion in vitro. A working cell bank can be generated by thawing and expanding cells from a master cell bank and then cryopreserving cells from the expanded population. In some embodiments, the expansion entails three or more rounds of passaging (e.g., clump passaging), e.g., three, four, five or more rounds of clump passaging. 6.2. Genomically Stabilized Populations of PSCs

[0073] The present disclosure provides genomically stabilized populations of PSCs.

[0074] The genomically stabilized populations have -and when differentiated can give rise to differentiated cells- with reduced tumorigenic potential as compared to populations of PSCs that are not genomically stabilized. Thus, the genomically stabilized populations are suitable for use in the production of cell therapy products with improved safety profiles.

[0075] Typically, the genomically stabilized populations have a reduced occurrence of genetic variants associated with increased tumorigenic potential, e.g., BCOR SNP1, BCOR SNP2, RARA SNP, or any combinations of two or all three of the foregoing.

[0076] In some embodiments, the prevalence of BCOR SNP1, BCOR SNP2 and RARA SNP in a genomically stabilized population is less than 1% each, e.g., VAF% of less than 1% each or less than 0.5% each. In some embodiments, the prevalence of BCOR SNP1, BCOR SNP2, and RARA SNP is each independently selected from lower than 0.5%, lower than 0.1%, or lower than 0.05%. In some embodiments, the prevalence of BCOR SNP1, BCOR SNP2 and RARA SNP is each independently about 0.9%, 0.8%, 0.7%, 0.6%, 0.5%, 0.4%, 0.3%, 0.2%, 0.1%, 0.05%, 0.01% or lower. In some embodiments, all SNPs are undetectable in a genomically stabilized population.

[0077] In some embodiments, the genomically stabilized population of pluripotent stem cells (PSCs) is a population of, or descended from an ancestral cell population comprising, induced pluripotent cells (iPSCs) or embryonic stem cells (ESC), preferably of human origin. Examples of suitable ancestral cell types are described in Section 6.7.

[0078] The genomically stabilized populations are typically the product of one or more expansions of the ancestral cell population and its progeny, and typically entail one or more rounds of cell banking prior differentiation into cells for therapeutic use.

[0079] Typically, prior to differentiation into cells for therapeutic use, a genomically stabilized population is the progeny of several rounds of expansion culture from the ancestral cell, e.g., at least two, at least three, at least four or at least five rounds of expansion culture.

[0080] One or more rounds of expansion culture are performed in the presence of a laminin moiety, e.g., as described in Section 6.6. In some embodiments, a majority, or all rounds, of expansion culture are performed in the presence of a laminin moiety. In certain embodiments, the one or more (or a majority or all) rounds of expansion culture are performed in the absence of (i) a vitronectin ( VTN, e.g., a recombinant VTN (e.g., recombinant human VTN), R&D-grade VTN, CTS-VTN, VTN-1 and / or VTN-2), (ii) a cadherin (e.g., e-cadherin), (iii) a feeder cell (e.g., fibroblasts), or (iv) any combination of two or all three of (i), (ii), and (iii).

[0081] In some embodiments, a majority of (optionally all) phases of a majority of (optionally all) expansions have been performed on a surface treated for increased PSC adherence, for example a surface is treated for increased hydrophilicity as described in Section 6.4.

[0082] Each round of expansion culture can entail multiple rounds of passaging, e.g., at least two, at least three or at least four rounds of passaging. In some embodiments, the passaging is clump passaging, e.g., in the presence of EDTA and / or in the absence of enzymatic (e.g., proteolytic / trypsin) treatment.

[0083] In some embodiments, a genomically stabilized population is the progeny of at least 6 cell passages in culture, at least 7 cell passages in culture, at least 8 cell passages in culture, at least 9 cell passages in culture, at least 10 cell passages in culture, at least 11 cell passages in culture, at least 12 cell passages in culture from the ancestral cell population, at least 13 cell passages in culture from the ancestral cell population, at least 14 cell passages in culture from the ancestral cell population, or at least 15 cell passages in culture, from the ancestral cell population. The passaging can represent one or more rounds of expansion culture, optionally separated by one or more cryopreservation and reactivation cycles.

[0084] The genomically stabilized population of the disclosure can be in the form of an in vitro cell culture, e.g., and an adherent cell culture optionally comprising at least one laminin moiety as described in Section 6.6, or cryopreserved, e.g., in a cryopreservation solution in a cryopreservation vial. 6.3. Methods for Producing Genomically Stabilized Populations of PSCs

[0085] The present disclosure further provides methods of producing genomically stabilized populations of PSCs, e.g., for differentiation into cells that are formulated for therapeutic use.

[0086] The genomically stabilized populations of PSCs are the progeny of an ancestral cell or cells from an ancestral cell population, e.g., as described in Section 6.7.

[0087] The genomically stabilized populations are typically produced by culturing an ancestral cell population and its progeny under expansion conditions. In some embodiments, culturing under expansion conditions comprises culturing under one or more and optionally all of the following conditions: (i) in the presence of a laminin moiety, e.g., as described in Section 6.6; (ii) suitable cell culture media, e.g., as described in Section 6.5; (iii) on a suitable cell culture container, e.g., as described in Section 6.4; (iv) utilizing clump passaging for one or more (or the majority or all) phases of expansion.

[0088] In some embodiments, cells from the ancestral cell population and its progeny undergo several rounds of expansion culture from the ancestral cell, e.g., at least two, at least three, at least four or at least five rounds of expansion culture to produce a genomically stabilized population of PSCs, e.g., for differentiation into cells that are formulated for therapeutic use.

[0089] In some embodiments, or more rounds of expansion culture are performed in the presence of a laminin moiety, e.g., as described in Section 6.6. In some embodiments, a majority, or all rounds, of expansion culture are performed in the presence of a laminin moiety. In certain embodiments, the one or more (or a majority or all) rounds of expansion culture are performed in the absence of (i) vitronectin (VTN, e.g., a recombinant VTN (e.g., recombinant human VTN), R&D-grade VTN, CTS-VTN, VTN-1 and / or VTN-2), (ii) cadherin (e.g., e- cadherin), (iii) a feeder cell (e.g., fibroblasts), or (iv) any combination of two or all three of (i), (ii), and (iii).

[0090] In some embodiments, a majority of (optionally all) phases of a majority of (optionally all) expansions are performed on a surface treated for increased PSC adherence, for example a surface is treated for increased hydrophilicity as described in Section 6.4.

[0091] Each round of expansion culture can entail multiple rounds of passaging, e.g., at least two, at least three or at least four rounds of passaging. In some embodiments, the passaging is clump passaging, e.g., in the presence of a chelator, such as EDTA, and / or in the absence of enzymatic (e.g., proteolytic / trypsin) treatment. An exemplary method of clump passaging is described in Section 8.1.3.

[0092] Clump passaging can include a step of removing non-adherent cells together with old cell culture medium, and adding a fresh cell culture medium to the remaining adherent cells prior to transferring to a new cell culture vessel. The cell culture medium can comprise one or more supplements, e.g., cell protection supplements. Exemplary cell protection supplements comprise ROCK inhibitors, such as Y-27632, Thiazovivin, and Chroman 1. Additional cell protection supplements are CloneR® and CloneR2®. In some embodiments, cell protection supplement comprises a cell protection supplement cocktail, for example comprising a ROCK inhibitor and one or more of additional supplements, such as a caspase inhibitor (e.g., Emricasan), one or more polyamines (e.g., a mixture of Putrescine, Spermine, andSpermidine), and / or an ISR inhibitor (e.g., trans-ISRIB). In some embodiments, the cell protection supplement cocktail is CEPT cocktail, which comprises Chroman1, Emricasan, polyamines, and trans-ISRIB. In some embodiments, cell protection supplement comprises a cell protection supplement cocktail containing a ROCK inhibitor and one or more additional cell protection supplements, such as an antioxidant and / or molecules that scavenge free radicals. In some embodiments, the cell protection supplement cocktail comprises Revitacell™, which comprises a ROCK inhibitor and molecules with antioxidant and free radical scavenger properties.

[0093] The cell culture medium comprising one or more supplements can, in some embodiments, be exchanged 18 to 30 hours (e.g., 20 hours, 24 hours, or 28 hours) after passaging, for example with a replacement cell culture media lacking the one or more supplements or comprising one or more supplements, e.g., cell protection supplements. Media exchanges can be complete (e.g., by removal of essentially all of the old cell culture medium before adding the new cell culture medium) or partial (e.g., by replacement of a portion of the old cell culture medium). A partial media exchange that replaces a portion of a cell culture medium comprising one or more supplements with a cell culture medium that lacks one or more of the supplements can be used to reduce the concentration of one or more supplements in the medium.

[0094] In some embodiments, methods of producing genomically stabilized populations of PSCs comprise subjecting cells of an ancestral cell population or its progeny to at least 5 cell passages in culture, at least 6 cell passages in culture, at least 7 cell passages in culture, at least 8 cell passages in culture, at least 9 cell passages in culture, at least 10 cell passages in culture, at least 11 cell passages in culture, at least 12 cell passages in culture from the ancestral cell population, at least 13 cell passages in culture from the ancestral cell population, at least 14 cell passages in culture from the ancestral cell population, or at least 15 cell passages in culture. The cumulative number of passages can represent multiple rounds of expansion.

[0095] Methods of producing genomically stabilized populations of PSCs may comprise one or more rounds of cryopreservation or cell banking, e.g., between the rounds of expansion. Prior to further culture (e.g., further expansion or differentiation), cryopreserved or banked populations of PSCs can be reactivated, e.g., by thawing, washing and pre-culturing under suitable conditions.

[0096] During the production of a genomically stabilized populations of PSCs, e.g., at one or more (the majority or all) phases of expansion, a PSC cell population can undergo testing for the presence or prevalence of one or more markers of tumorigenic potential, e.g., BCOR SNP1, BCOR SNP2 and / or RARA SNP. If it is determined that the prevalence of the one or more markers of tumorigenic potential exceeds a certain threshold, the PSC cell population can bediscarded. Alternatively, cells from the PSC cell population can continue to be cultured under the expansion conditions described herein, such that a genomically stabilized cell population in which one or more markers of tumorigenic potential is below a desired threshold is produced.

[0097] The threshold value used for one or more markers of tumorigenic potential is typically a certain percentage value (e.g., 1%, 0.05%, etc.). The threshold value of a SNP can be based on the prevalence percentage of that SNP in the cell population and / or on the variant allele frequency (VAF) that corresponds to that SNP.

[0098] In some embodiments, the threshold value of a SNP located on the X chromosome (e.g., BCOR SNP1 and / or BCOR SNP2) can be based on a prevalence percentage of that SNP in the cell population. Additionally or alternatively, the threshold value of a SNP can also be based on the VAF. In some embodiments, the VAF-based threshold value is dependent on the number of X chromosomes in the cells of the population. In other embodiments, the VAF-based threshold value is independent of the number of X chromosomes in the cells of the population. Particularly, male cells have only one X chromosome, and female cells have two X chromosomes with one copy of the X chromosome inactivated as a result of XCI. Therefore, SNPs in genes located on the X chromosome having a particular prevalence will have different VAF values in male and female cell populations. For example, if a SNP in an X-linked gene is present in 1% of cells in a cell population, its VAF will differ depending on whether the cell population is a male or female cell population. In a male cell population, the VAF is also 1% because, while in a female cell population the VAF is 0.5% due to the presence of a second copy of the X chromosome gene. In some embodiments, a VAF-based threshold value of a SNP located on the X chromosome (e.g., BCOR SNP1 and / or BCOR SNP2) is the same in male cell populations and female cell populations (e.g., 1%, 0.5%, 0.1%, 0.05% or 0.01%, irrespective of whether the cell population is male or female. In other embodiments, a VAF- based threshold value of a SNP located on the X chromosome is dependent on whether the cell population is male or female, e.g., with the threshold value in male cell populations twice that of the threshold value in female cell populations. For example, in some embodiments, the threshold value is less than 1%, 0.5%, 0.1%, 0.05% or 0.01% in a female cell population and less than 2%, 1%, 0.2%, 0.1%, or 0.02%, respectively, in a male cell population.

[0099] The resulting genomically stabilized population can be in the form of an in vitro cell culture (e.g., and an adherent cell culture optionally comprising at least one laminin moiety as described in Section 6.6) or cryopreserved (e.g., in a cryopreservation solution in a cryopreservation vial).

[0100] An exemplary process for producing genomically stabilized population of cells is shown in FIG.11.6.4. Cell Culture Containers and Substrates

[0101] Without being bound by theory, the inventors believe that the substrate on which PSCs are cultured can impact whether or not tumorigenic genetic variants emerge during expansion culture and therefore whether or not a genomically stabilized cell population is produced under conditions of PSC expansion.

[0102] Cell culture containers may be uncoated and / or untreated or coated and / or treated on at least a part of their internal surface (typically either the whole of their internal surface or at least the part of their internal surface that will form the bottom surface of the container in use). Coatings can be applied without covalent bonds (also referred to as passive coatings) or can be bound covalently with the surface on which it is applied. Non-covalent coatings commonly used for cell culture containers include but are not limited to phospholipids, streptavidin, antibodies, collagen I and Poly-d-lysine (PDL). These coatings can be used alone or in combinations. Covalent coatings commonly used for cell culture containers include some streptavidin coatings, nickel chelate, protein A, WGA (wheat germ agglutinin) and hydrogels. Surfaces of containers can be treated, for example, using energy-based methods (e.g., plasma treatment), to change the physico-chemical properties of the surface. For example, the surface of a container can be treated to increase its hydrophilic character, which may help to improve cell adhesion as materials such as polystyrene are typically hydrophobic when untreated. Examples of such surface treatments include the Nunclon™ Delta surface treatment from Thermo Scientific™, TC-treated cell culture flasks from Azer Scientific, and Corning™ TC- treated labware.

[0103] In some embodiments, PSCs are cultured in cell culture containers that are treated to improve adhesion to the substrate of the containers.

[0104] In some embodiments, the substrate is a tissue culture plastic (a polystyrene) coated for increased hydrophilicity.

[0105] In some embodiments, the substrate is a tissue culture plastic (a polystyrene) treated with Nunclon™ Delta surface treatment from Thermo Scientific™ or an equivalent treatment, e.g., as described in U.S. Patent No.10,066,203 B2, which is incorporated by reference herein in its entirety.

[0106] In some embodiments, the substrate is a TC-treated cell culture flasks from Azer Scientific or tissue culture plastic (a polystyrene) treated with an equivalent treatment.

[0107] In some embodiments, the substrate is a tissue culture plastic (a polystyrene) coated polydopamine.

[0108] In some embodiments, the substrate is coated with a laminin moiety, e.g., as described in Section 6.6.

[0109] In some embodiments, the substrate is not coated with a vitronectin (VTN, e.g., a recombinant VTN, R&D-grade VTN, CTS-VTN, VTN-1 and / or VTN-2) and / or does not contain a vitronectin (VTN, e.g., a recombinant VTN, R&D-grade VTN, CTS-VTN, VTN-1 and / or VTN-2).

[0110] In some embodiments, the substrate is not coated with a cadherin (e.g., e-cadherin) and / or does not comprise a cadherin (e.g., e-cadherin).

[0111] In some embodiments, the substrate does not comprise feeder cells or a feeder cell layer, e.g., fibroblast feeder cells or a fibroblast feeder cell layer. 6.5. Expansion Culture Media

[0112] The genomically stabilized populations of PSCs of the disclosure are the progeny of one or more rounds of expansion culture.

[0113] In some embodiments, the expansion culture is performed with cell culture media that support pluripotent stem cell maintenance and expansion. In some embodiments, the cell culture media comprise a basal medium, e.g., DMEM / F12, and one or more additional components, e.g., one or more additional components as described in this Section.

[0114] In some embodiments, the cell culture media comprise DMEM / F12 or other like medium.

[0115] In some embodiments, the cell culture media comprise DMEM / F12 or other like medium and any one or more of transferrin, insulin, FGF, and TGFβ.

[0116] In some embodiments, the cell culture media do not comprise albumin.

[0117] In some embodiments, the culture media comprise fibroblast growth factor 2 (FGF2), e.g., heat-stabilized FGF2.

[0118] In some embodiments, the culture media comprise basic fibroblast growth factor (e.g., recombinant human (rh) bFGF), or TGFβ (e.g., rh TGFβ), or a combination thereof.

[0119] In some embodiments, the culture media comprise stabilized FGF2, TGF-β1, insulin, human serum albumin, a buffer, LiCl, L-ascorbic acid, or a combination thereof, e.g., FGF2, TGF-β1, insulin, human serum albumin, a buffer, LiCl, and L-ascorbic acid.

[0120] In some embodiments, the culture media comprise stabilized FGF2, TGF-β1 or Activin A, insulin or insulin-like growth factor 1 (IGF-1), a buffer, antioxidants, or a combination thereof, e.g., stabilized FGF2, TGF-β1 or Activin A, insulin or IGF-1, a buffer, and antioxidants. In some embodiments, the culture media comprise FGF2, TGF-β1, and insulin. In some embodiments, the culture media comprise FGF2, TGF-β1, and IGF-1. In some embodiments, the culture media comprise FGF2, Activin A, and insulin. In some embodiments, the culture media comprise FGF2, Activin A, and IGF-1.

[0121] some embodiments, the culture media comprise FGF2, TGF-β1 or Nodal, insulin, transferrin, L-ascorbic acid 2-phosphate, sodium selenite, sodium bicarbonate, or a combination thereof, e.g., FGF2, TGF-β1 or Nodal, insulin, transferrin, L-ascorbic acid 2- phosphate, sodium selenite, and sodium bicarbonate. In some embodiments, the media comprise FGF2, TGF-β1, insulin, transferrin, L-ascorbic acid 2-phosphate, sodium selenite, and sodium bicarbonate. In some embodiments, the media comprise FGF2, Nodal, insulin, transferrin, L-ascorbic acid 2-phosphate, sodium selenite, and sodium bicarbonate.

[0122] In some embodiments, the culture media comprise FGF2, TGF-β1, insulin, human serum albumin, transferrin, LiCl, L-ascorbic acid, or a combination thereof, e.g., FGF2, TGF-β1, insulin, human serum albumin, transferrin, LiCl, and L-ascorbic acid.

[0123] The cell culture media are not limited to any specific media or base media formulation so long as the media or base media formulation supports pluripotent stem cell maintenance and expansion. Examples of useful media or base media formulations include TeSR™ pluripotent stem cell culture media, eTeSR™ maintenance medium (Stemcell Technologies, cat. no.100- 1215) , mTeSR™ Plus (Stemcell Technologies, cat. no.100-1130), StemSpan™ hematopoietic cell media (Stemcell Technologies, Cambridge, MA); NutriStem® hPSC xeno-free defined culture media, NutriStem® hMSC xeno-free defined culture media (Sartorius, Goettingen, DE); PluriSTEM® Human ES / iPS Cell Medium defined small molecule based serum-free medium, PluriSTEM-XF® Human ES / iPS Cell Medium complete xeno-free medium (Millipore Sigma, St. Louis, MO); basal media such as RPMI (Roosevelt Park Memorial Institute) media, BME (Eagle’s Basal Medium), MEM (Modified Eagle’s Medium), DMEM (Dulbecco’s Modified Eagle’s Medium), DMEM / F12 media, IMDM (Iscove Modified Dulbecco Media), IMDM / F12, Essential 8 (E8), TeSR-E8, mTeSR™1 (Stemcell Technologies cat. no.85850), TeSR™ AOF, iPS-Brew, StemMACS™ iPS Brew XF™, StemFit®, StemFlex™, CTS™ StemScale™, or ExCellerate™; media with or without growth factors, serum-free media, chemically defined media, xeno-free media, animal component-free media, complete media; and the like.

[0124] In some embodiments, the medium comprises mTeSR™ 1 medium. In some embodiments, the medium comprises ExCellerate™ medium.

[0125] In some embodiments, the same cell culture media are utilized at all phases of all rounds of expansion culture.

[0126] In some embodiments, different cell culture media are utilized at different phases and / or different rounds of expansion culture.

[0127] In some embodiments, the cell culture media (i) comprises a laminin moiety (e.g., as described in Section 6.6), (ii) lacks a vitronectin (VTN, e.g., a recombinant VTN, R&D-grade VTN, CTS-VTN, VTN-1 and / or VTN-2), (iii) lacks a cadherin (e.g., e-cadherin), (iv) lacks cellsother than PSCs (e.g., lacks cells from a feeder cell layer such as fibroblasts), or (iv) has any combination of two, three or all four features defined in (i)-(iv). 6.6. Laminin Moiety

[0128] The genomically stabilized populations of PSCs of the disclosure are typically produced by expansion culture in the presence of a laminin moiety. In some embodiments, a laminin moiety is a laminin polypeptide or a fragment thereof.

[0129] Laminins are large multidomain glycoproteins with a common structural organization. In vivo, laminins reside primarily in the basal lamina and integrate various matrix and cell interactive functions, including but not limited to, cell signaling, maintaining cell / tissue phenotype, and promoting cell growth and differentiation in tissue repair and development.

[0130] Typically, laminin is a trimeric protein comprising one alpha chain (laminin α-chain; herein also referred to as LAMA chain) subunit, one beta chain (laminin β-chain; herein also referred to as LAMB chain) subunit, and one gamma chain (laminin γ-chain; herein also referred to as LAMC chain) subunit. There are at least five α-chains, three β-chains and three γ- chains that have been characterized. These known subunit chains form at least 15 distinct laminin types in tissues, which are termed laminin-1 to laminin-15 based on the order of their characterization, but an alternative nomenclature describes the isoforms based on their subunit composition. For instance, laminin-111 (laminin-1) contains laminin alpha-1, laminin beta-1 and laminin gamma-1 chains, which is often denoted as α1β1γ1.

[0131] Four structurally defined family groups of laminins have been identified. The first group of five identified laminins all share the β1 and γ1 subunits, and vary by their α-chain composition (α1 to α5 chain). The second group of five identified laminins all share the β2 and γ1 chain, vary by their α-chain composition (α1 to α5 chain). The third group of identified laminin molecules has one identified member, laminin-332, with a chain composition of α3β3γ2. The fourth group of identified laminin molecules has one identified member, laminin-213, with a chain composition of α2β1γ3.

[0132] In some embodiments, the laminin moiety comprises a laminin alpha chain or fragment thereof. In some embodiments the laminin moiety comprises a laminin beta chain or a fragment thereof. In some embodiments, the laminin moiety comprises a laminin gamma chain or a fragment thereof. In some embodiments, the laminin moiety comprises a laminin alpha polypeptide or fragment thereof; a laminin alpha polypeptide and a laminin gamma polypeptide or fragments thereof; and / or a laminin alpha polypeptide, beta polypeptide, and gamma polypeptide or fragments thereof.

[0133] In some embodiments, the laminin moiety is a laminin alpha 5 (α5 or LAMA5) polypeptide or fragment thereof. The full-length amino acid sequence of a representative human laminin alpha 5 chain is set forth below, with the signal sequence underlined.MAKRLCAGSA LCVRGPRGPA PLLLVGLALL GAARAREEAG GGFSLHPPYF NLAEGARIAA SATCGEEAPA RGSPRPTEDL YCKLVGGPVA GGDPNQTIRG QYCDICTAAN SNKAHPASNA IDGTERWWQS PPLSRGLEYN EVNVTLDLGQ VFHVAYVLIK FANSPRPDLW VLERSMDFGR TYQPWQFFAS SKRDCLERFG PQTLERITRD DAAICTTEYS RIVPLENGEI VVSLVNGRPG AMNFSYSPLL REFTKATNVR LRFLRTNTLL GHLMGKALRD PTVTRRYYYS IKDISIGGRC VCHGHADACD AKDPTDPFRL QCTCQHNTCG GTCDRCCPGF NQQPWKPATA NSANECQSCN CYGHATDCYY DPEVDRRRAS QSLDGTYQGG GVCIDCQHHT TGVNCERCLP GFYRSPNHPL DSPHVCRRCN CESDFTDGTC EDLTGRCYCR PNFSGERCDV CAEGFTGFPS CYPTPSSSND TREQVLPAGQ IVNCDCSAAG TQGNACRKDP RVGRCLCKPN FQGTHCELCA PGFYGPGCQP CQCSSPGVAD DRCDPDTGQC RCRVGFEGAT CDRCAPGYFH FPLCQLCGCS PAGTLPEGCD EAGRCLCQPE FAGPHCDRCR PGYHGFPNCQ ACTCDPRGAL DQLCGAGGLC RCRPGYTGTA CQECSPGFHG FPSCVPCHCS AEGSLHAACD PRSGQCSCRP RVTGLRCDTC VPGAYNFPYC EAGSCHPAGL APVDPALPEA QVPCMCRAHV EGPSCDRCKP GFWGLSPSNP EGCTRCSCDL RGTLGGVAEC QPGTGQCFCK PHVCGQACAS CKDGFFGLDQ ADYFGCRSCR CDIGGALGQS CEPRTGVCRC RPNTQGPTCS EPARDHYLPD LHHLRLELEE AATPEGHAVR FGFNPLEFEN FSWRGYAQMA PVQPRIVARL NLTSPDLFWL VFRYVNRGAM SVSGRVSVRE EGRSATCANC TAQSQPVAFP PSTEPAFITV PQRGFGEPFV LNPGTWALRV EAEGVLLDYV VLLPSAYYEA ALLQLRVTEA CTYRPSAQQS GDNCLLYTHL PLDGFPSAAG LEALCRQDNS LPRPCPTEQL SPSHPPLITC TGSDVDVQLQ VAVPQPGRYA LVVEYANEDA RQEVGVAVHT PQRAPQQGLL SLHPCLYSTL CRGTARDTQD HLAVFHLDSE ASVRLTAEQA RFFLHGVTLV PIEEFSPEFV EPRVSCISSH GAFGPNSAAC LPSRFPKPPQ PIILRDCQVI PLPPGLPLTH AQDLTPAMSP AGPRPRPPTA VDPDAEPTLL REPQATVVFT THVPTLGRYA FLLHGYQPAH PTFPVEVLIN AGRVWQGHAN ASFCPHGYGC RTLVVCEGQA LLDVTHSELT VTVRVPKGRW LWLDYVLVVP ENVYSFGYLR EEPLDKSYDF ISHCAAQGYH ISPSSSSLFC RNAAASLSLF YNNGARPCGC HEVGATGPTC EPFGGQCPCH AHVIGRDCSR CATGYWGFPN CRPCDCGARL CDELTGQCIC PPRTIPPDCL LCQPQTFGCH PLVGCEECNC SGPGIQELTD PTCDTDSGQC KCRPNVTGRR CDTCSPGFHG YPRCRPCDCH EAGTAPGVCD PLTGQCYCKE NVQGPKCDQC SLGTFSLDAA NPKGCTRCFC FGATERCRSS SYTRQEFVDM EGWVLLSTDR QVVPHERQPG TEMLRADLRH VPEAVPEAFP ELYWQAPPSY LGDRVSSYGG TLRYELHSET QRGDVFVPME SRPDVVLQGN QMSITFLEPA YPTPGHVHRG QLQLVEGNFR HTETRNTVSR EELMMVLASL EQLQIRALFS QISSAVFLRR VALEVASPAG QGALASNVEL CLCPASYRGD SCQECAPGFY RDVKGLFLGR CVPCQCHGHS DRCLPGSGVC VDCQHNTEGA HCERCQAGFV SSRDDPSAPC VSCPCPLSVP SNNFAEGCVL RGGRTQCLCK PGYAGASCER CAPGFFGNPL VLGSSCQPCD CSGNGDPNLL FSDCDPLTGA CRGCLRHTTG PRCEICAPGF YGNALLPGNC TRCDCTPCGT EACDPHSGHC LCKAGVTGRR CDRCQEGHFG FDGCGGCRPC ACGPAAEGSE CHPQSGQCHC RPGTMGPQCR ECAPGYWGLP EQGCRRCQCP GGRCDPHTGR CNCPPGLSGE RCDTCSQQHQ VPVPGGPVGH SIHCEVCDHC VVLLLDDLER AGALLPAIHE QLRGINASSM AWARLHRLNA SIADLQSQLR SPLGPRHETA QQLEVLEQQS TSLGQDARRL GGQAVGTRDQ ASQLLAGTEA TLGHAKTLLA AIRAVDRTLS ELMSQTGHLG LANASAPSGE QLLRTLAEVE RLLWEMRARD LGAPQAAAEA ELAAAQRLLA RVQEQLSSLW EENQALATQT RDRLAQHEAG LMDLREALNR AVDATREAQE LNSRNQERLE EALQRKQELS RDNATLQATL HAARDTLASV FRLLHSLDQA KEELERLAAS LDGARTPLLQ RMQTFSPAGS KLRLVEAAEA HAQQLGQLAL NLSSIILDVN QDRLTQRAIE ASNAYSRILQ AVQAAEDAAG QALQQADHTW ATVVRQGLVD RAQQLLANST ALEEAMLQEQ QRLGLVWAAL QGARTQLRDV RAKKDQLEAH IQAAQAMLAM DTDETSKKIA HAKAVAAEAQ DTATRVQSQL QAMQENVERW QGQYEGLRGQ DLGQAVLDAG HSVSTLEKTL PQLLAKLSIL ENRGVHNASL ALSASIGRVR ELIAQARGAA SKVKVPMKFN GRSGVQLRTP RDLADLAAYT ALKFYLQGPE PEPGQGTEDR FVMYMGSRQA TGDYMGVSLR DKKVHWVYQL GEAGPAVLSI DEDIGEQFAA VSLDRTLQFG HMSVTVERQM IQETKGDTVA PGAEGLLNLR PDDFVFYVGG YPSTFTPPPL LRFPGYRGCI EMDTLNEEVV SLYNFERTFQ LDTAVDRPCA RSKSTGDPWL TDGSYLDGTG FARISFDSQI STTKRFEQEL RLVSYSGVLF FLKQQSQFLC LAVQEGSLVL LYDFGAGLKK AVPLQPPPPL TSASKAIQVF LLGGSRKRVL VRVERATVYS VEQDNDLELA DAYYLGGVPP DQLPPSLRRL FPTGGSVRGC VKGIKALGKY VDLKRLNTTG VSAGCTADLL VGRAMTFHGH GFLRLALSNV APLTGNVYSG FGFHSAQDSA LLYYRASPDG LCQVSLQQGR VSLQLLRTEV KTQAGFADGA PHYVAFYSNA TGVWLYVDDQ LQQMKPHRGP PPELQPQPEG PPRLLLGGLP ESGTIYNFSG CISNVFVQRL LGPQRVFDLQ QNLGSVNVST GCAPALQAQT PGLGPRGLQA TARKASRRSR QPARHPACML PPHLRTTRDS YQFGGSLSSH LEFVGILARHRNWPSLSMHV LPRSSRGLLL FTARLRPGSP SLALFLSNGH FVAQMEGLGT RLRAQSRQRS RPGRWHKVSV RWEKNRILLV TDGARAWSQE GPHRQHQGAE HPQPHTLFVG GLPASSHSSK LPVTVGFSGC VKRLRLHGRP LGAPTRMAGV TPCILGPLEA GLFFPGSGGV ITLDLPGATL PDVGLELEVR PLAVTGLIFH LGQARTPPYL QLQVTEKQVL LRADDGAGEF STSVTRPSVL CDGQWHRLAV MKSGNVLRLE VDAQSNHTVG PLLAAAAGAP APLYLGGLPE PMAVQPWPPA YCGCMRRLAV NRSPVAMTRS VEVHGAVGAS GCPAA (SEQ ID NO:1)

[0134] In some embodiments, the laminin moiety comprises an amino acid sequence having at least 75% sequence identity to the mature human laminin alpha 5 (α5 or LAMA5) polypeptide chain or fragment thereof. The mature amino acid sequence of the human laminin alpha 5 chain represented by SEQ ID NO:1 is set forth below. REEAG GGFSLHPPYF NLAEGARIAA SATCGEEAPA RGSPRPTEDL YCKLVGGPVA GGDPNQTIRG QYCDICTAAN SNKAHPASNA IDGTERWWQS PPLSRGLEYN EVNVTLDLGQ VFHVAYVLIK FANSPRPDLW VLERSMDFGR TYQPWQFFAS SKRDCLERFG PQTLERITRD DAAICTTEYS RIVPLENGEI VVSLVNGRPG AMNFSYSPLL REFTKATNVR LRFLRTNTLL GHLMGKALRD PTVTRRYYYS IKDISIGGRC VCHGHADACD AKDPTDPFRL QCTCQHNTCG GTCDRCCPGF NQQPWKPATA NSANECQSCN CYGHATDCYY DPEVDRRRAS QSLDGTYQGG GVCIDCQHHT TGVNCERCLP GFYRSPNHPL DSPHVCRRCN CESDFTDGTC EDLTGRCYCR PNFSGERCDV CAEGFTGFPS CYPTPSSSND TREQVLPAGQ IVNCDCSAAG TQGNACRKDP RVGRCLCKPN FQGTHCELCA PGFYGPGCQP CQCSSPGVAD DRCDPDTGQC RCRVGFEGAT CDRCAPGYFH FPLCQLCGCS PAGTLPEGCD EAGRCLCQPE FAGPHCDRCR PGYHGFPNCQ ACTCDPRGAL DQLCGAGGLC RCRPGYTGTA CQECSPGFHG FPSCVPCHCS AEGSLHAACD PRSGQCSCRP RVTGLRCDTC VPGAYNFPYC EAGSCHPAGL APVDPALPEA QVPCMCRAHV EGPSCDRCKP GFWGLSPSNP EGCTRCSCDL RGTLGGVAEC QPGTGQCFCK PHVCGQACAS CKDGFFGLDQ ADYFGCRSCR CDIGGALGQS CEPRTGVCRC RPNTQGPTCS EPARDHYLPD LHHLRLELEE AATPEGHAVR FGFNPLEFEN FSWRGYAQMA PVQPRIVARL NLTSPDLFWL VFRYVNRGAM SVSGRVSVRE EGRSATCANC TAQSQPVAFP PSTEPAFITV PQRGFGEPFV LNPGTWALRV EAEGVLLDYV VLLPSAYYEA ALLQLRVTEA CTYRPSAQQS GDNCLLYTHL PLDGFPSAAG LEALCRQDNS LPRPCPTEQL SPSHPPLITC TGSDVDVQLQ VAVPQPGRYA LVVEYANEDA RQEVGVAVHT PQRAPQQGLL SLHPCLYSTL CRGTARDTQD HLAVFHLDSE ASVRLTAEQA RFFLHGVTLV PIEEFSPEFV EPRVSCISSH GAFGPNSAAC LPSRFPKPPQ PIILRDCQVI PLPPGLPLTH AQDLTPAMSP AGPRPRPPTA VDPDAEPTLL REPQATVVFT THVPTLGRYA FLLHGYQPAH PTFPVEVLIN AGRVWQGHAN ASFCPHGYGC RTLVVCEGQA LLDVTHSELT VTVRVPKGRW LWLDYVLVVP ENVYSFGYLR EEPLDKSYDF ISHCAAQGYH ISPSSSSLFC RNAAASLSLF YNNGARPCGC HEVGATGPTC EPFGGQCPCH AHVIGRDCSR CATGYWGFPN CRPCDCGARL CDELTGQCIC PPRTIPPDCL LCQPQTFGCH PLVGCEECNC SGPGIQELTD PTCDTDSGQC KCRPNVTGRR CDTCSPGFHG YPRCRPCDCH EAGTAPGVCD PLTGQCYCKE NVQGPKCDQC SLGTFSLDAA NPKGCTRCFC FGATERCRSS SYTRQEFVDM EGWVLLSTDR QVVPHERQPG TEMLRADLRH VPEAVPEAFP ELYWQAPPSY LGDRVSSYGG TLRYELHSET QRGDVFVPME SRPDVVLQGN QMSITFLEPA YPTPGHVHRG QLQLVEGNFR HTETRNTVSR EELMMVLASL EQLQIRALFS QISSAVFLRR VALEVASPAG QGALASNVEL CLCPASYRGD SCQECAPGFY RDVKGLFLGR CVPCQCHGHS DRCLPGSGVC VDCQHNTEGA HCERCQAGFV SSRDDPSAPC VSCPCPLSVP SNNFAEGCVL RGGRTQCLCK PGYAGASCER CAPGFFGNPL VLGSSCQPCD CSGNGDPNLL FSDCDPLTGA CRGCLRHTTG PRCEICAPGF YGNALLPGNC TRCDCTPCGT EACDPHSGHC LCKAGVTGRR CDRCQEGHFG FDGCGGCRPC ACGPAAEGSE CHPQSGQCHC RPGTMGPQCR ECAPGYWGLP EQGCRRCQCP GGRCDPHTGR CNCPPGLSGE RCDTCSQQHQ VPVPGGPVGH SIHCEVCDHC VVLLLDDLER AGALLPAIHE QLRGINASSM AWARLHRLNA SIADLQSQLR SPLGPRHETA QQLEVLEQQS TSLGQDARRL GGQAVGTRDQ ASQLLAGTEA TLGHAKTLLA AIRAVDRTLS ELMSQTGHLG LANASAPSGE QLLRTLAEVE RLLWEMRARD LGAPQAAAEA ELAAAQRLLA RVQEQLSSLW EENQALATQT RDRLAQHEAG LMDLREALNR AVDATREAQE LNSRNQERLE EALQRKQELS RDNATLQATL HAARDTLASV FRLLHSLDQA KEELERLAAS LDGARTPLLQ RMQTFSPAGS KLRLVEAAEA HAQQLGQLAL NLSSIILDVN QDRLTQRAIE ASNAYSRILQ AVQAAEDAAG QALQQADHTW ATVVRQGLVD RAQQLLANST ALEEAMLQEQ QRLGLVWAAL QGARTQLRDV RAKKDQLEAH IQAAQAMLAM DTDETSKKIA HAKAVAAEAQ DTATRVQSQL QAMQENVERW QGQYEGLRGQDLGQAVLDAG HSVSTLEKTL PQLLAKLSIL ENRGVHNASL ALSASIGRVR ELIAQARGAA SKVKVPMKFN GRSGVQLRTP RDLADLAAYT ALKFYLQGPE PEPGQGTEDR FVMYMGSRQA TGDYMGVSLR DKKVHWVYQL GEAGPAVLSI DEDIGEQFAA VSLDRTLQFG HMSVTVERQM IQETKGDTVA PGAEGLLNLR PDDFVFYVGG YPSTFTPPPL LRFPGYRGCI EMDTLNEEVV SLYNFERTFQ LDTAVDRPCA RSKSTGDPWL TDGSYLDGTG FARISFDSQI STTKRFEQEL RLVSYSGVLF FLKQQSQFLC LAVQEGSLVL LYDFGAGLKK AVPLQPPPPL TSASKAIQVF LLGGSRKRVL VRVERATVYS VEQDNDLELA DAYYLGGVPP DQLPPSLRRL FPTGGSVRGC VKGIKALGKY VDLKRLNTTG VSAGCTADLL VGRAMTFHGH GFLRLALSNV APLTGNVYSG FGFHSAQDSA LLYYRASPDG LCQVSLQQGR VSLQLLRTEV KTQAGFADGA PHYVAFYSNA TGVWLYVDDQ LQQMKPHRGP PPELQPQPEG PPRLLLGGLP ESGTIYNFSG CISNVFVQRL LGPQRVFDLQ QNLGSVNVST GCAPALQAQT PGLGPRGLQA TARKASRRSR QPARHPACML PPHLRTTRDS YQFGGSLSSH LEFVGILARH RNWPSLSMHV LPRSSRGLLL FTARLRPGSP SLALFLSNGH FVAQMEGLGT RLRAQSRQRS RPGRWHKVSV RWEKNRILLV TDGARAWSQE GPHRQHQGAE HPQPHTLFVG GLPASSHSSK LPVTVGFSGC VKRLRLHGRP LGAPTRMAGV TPCILGPLEA GLFFPGSGGV ITLDLPGATL PDVGLELEVR PLAVTGLIFH LGQARTPPYL QLQVTEKQVL LRADDGAGEF STSVTRPSVL CDGQWHRLAV MKSGNVLRLE VDAQSNHTVG PLLAAAAGAP APLYLGGLPE PMAVQPWPPA YCGCMRRLAV NRSPVAMTRS VEVHGAVGAS GCPAA (SEQ ID NO:31)

[0135] In some embodiments, the laminin moiety comprises an amino acid sequence having at least 76% sequence identity, at least 77% sequence identity, at least 78% sequence identity, at least 79% sequence identity, at least 80% sequence identity, at least 81% sequence identity, at least 82% sequence identity, at least 83% sequence identity, at least 84% sequence identity, at least 85% sequence identity, at least 86% sequence identity, at least 87% sequence identity, at least 88% sequence identity, at least 89% sequence identity, at least 90% sequence identity at least 91% sequence identity, at least 92% sequence identity, at least 93% sequence identity, at least 94% sequence identity, at least 95% sequence identity, at least 96% sequence identity, at least 97% sequence identity, at least 98% sequence identity, at least 99% sequence identity or 100% sequence identity to the amino acid sequence of SEQ ID NO:31 or a fragment thereof that supports adhesion of PSCs to a substrate.

[0136] In some embodiments, the laminin moiety is a laminin alpha 5 chain X2 variant or a fragment thereof. The full-length amino acid sequence of a representative human laminin alpha 5 chain X2 variant is set forth below, with the signal sequence underlined. MAKRLCAGSA LCVRGPRGPA PLLLVGLALL GAARAREEAG GGFSLHPPYF NLAEGARIAA SATCGEEAPA RGSPRPTEDL YCKLVGGPVA GGDPNQTIRG QYCDICTAAN SNKAHPASNA IDGTERWWQS PPLSRGLEYN EVNVTLDLGQ VFHVAYVLIK FANSPRPDLW VLERSMDFGR TYQPWQFFAS SKRDCLERFG PQTLERITRD DAAICTTEYS RIVPLENGEI VVSLVNGRPG AMNFSYSPLL REFTKATNVR LRFLRTNTLL GHLMGKALRD PTVTRRYYYS IKDISIGGRC VCHGHADACD AKDPTDPFRL QCTCQHNTCG GTCDRCCPGF NQQPWKPATA NSANECQSCN CYGHATDCYY DPEVDRRRAS QSLDGTYQGG GVCIDCQHHT TGVNCERCLP GFYRSPNHPL DSPHVCRRCN CESDFTDGTC EDLTGRCYCR PNFSGERCDV CAEGFTGFPS CYPTPSSSND TREQVLPAGQ IVNCDCSAAG TQGNACRKDP RVGRCLCKPN FQGTHCELCA PGFYGPGCQP CQCSSPGVAD DRCDPDTGQC RCRVGFEGAT CDRCAPGYFH FPLCQLCGCS PAGTLPEGCD EAGRCLCQPE FAGPHCDRCR PGYHGFPNCQ ACTCDPRGAL DQLCGAGGLC RCRPGYTGTA CQECSPGFHG FPSCVPGSCH PAGLAPVDPA LPEAQVPCMC RAHVEGPSCD RCKPGFWGLS PSNPEGCTRC SCDLRGTLGG VAECQPGTGQ CFCKPHVCGQ ACASCKDGFF GLDQADYFGC RSCRCDIGGA LGQSCEPRTG VCRCRPNTQG PTCSEPARDH YLPDLHHLRL ELEEAATPEG HAVRFGFNPL EFENFSWRGY AQMAPVQPRI VARLNLTSPD LFWLVFRYVN RGAMSVSGRV SVREEGRSAT CANCTAQSQP VAFPPSTEPA FITVPQRGFG EPFVLNPGTW ALRVEAEGVLLDYVVLLPSA YYEAALLQLR VTEACTYRPS AQQSGDNCLL YTHLPLDGFP SAAGLEALCR QDNSLPRPCP TEQLSPSHPP LITCTGSDVD VQLQVAVPQP GRYALVVEYA NEDARQEVGV AVHTPQRAPQ QGLLSLHPCL YSTLCRGTAR DTQDHLAVFH LDSEASVRLT AEQARFFLHG VTLVPIEEFS PEFVEPRVSC ISSHGAFGPN SAACLPSRFP KPPQPIILRD CQVIPLPPGL PLTHAQDLTP AMSPAGPRPR PPTAVDPDAE PTLLREPQAT VVFTTHVPTL GRYAFLLHGY QPAHPTFPVE VLINAGRVWQ GHANASFCPH GYGCRTLVVC EGQALLDVTH SELTVTVRVP KGRWLWLDYV LVVPENVYSF GYLREEPLDK SYDFISHCAA QGYHISPSSS SLFCRNAAAS LSLFYNNGAR PCGCHEVGAT GPTCEPFGGQ CPCHAHVIGR DCSRCATGYW GFPNCRPCDC GARLCDELTG QCICPPRTIP PDCLLCQPQT FGCHPLVGCE ECNCSGPGIQ ELTDPTCDTD SGQCKCRPNV TGRRCDTCSP GFHGYPRCRP CDCHEAGTAP GVCDPLTGQC YCKENVQGPK CDQCSLGTFS LDAANPKGCT RCFCFGATER CRSSSYTRQE FVDMEGWVLL STDRQVVPHE RQPGTEMLRA DLRHVPEAVP EAFPELYWQA PPSYLGDRVS SYGGTLRYEL HSETQRGDVF VPMESRPDVV LQGNQMSITF LEPAYPTPGH VHRGQLQLVE GNFRHTETRN TVSREELMMV LASLEQLQIR ALFSQISSAV FLRRVALEVA SPAGQGALAS NVELCLCPAS YRGDSCQECA PGFYRDVKGL FLGRCVPCQC HGHSDRCLPG SGVCVDCQHN TEGAHCERCQ AGFVSSRDDP SAPCVSCPCP LSVPSNNFAE GCVLRGGRTQ CLCKPGYAGA SCERCAPGFF GNPLVLGSSC QPCDCSGNGD PNLLFSDCDP LTGACRGCLR HTTGPRCEIC APGFYGNALL PGNCTRCDCT PCGTEACDPH SGHCLCKAGV TGRRCDRCQE GHFGFDGCGG CRPCACGPAA EGSECHPQSG QCHCRPGTMG PQCRECAPGY WGLPEQGCRR CQCPGGRCDP HTGRCNCPPG LSGERCDTCS QQHQVPVPGG PVGHSIHCEV CDHCVVLLLD DLERAGALLP AIHEQLRGIN ASSMAWARLH RLNASIADLQ SQLRSPLGPR HETAQQLEVL EQQSTSLGQD ARRLGGQAVG TRDQASQLLA GTEATLGHAK TLLAAIRAVD RTLSELMSQT GHLGLANASA PSGEQLLRTL AEVERLLWEM RARDLGAPQA AAEAELAAAQ RLLARVQEQL SSLWEENQAL ATQTRDRLAQ HEAGLMDLRE ALNRAVDATR EAQELNSRNQ ERLEEALQRK QELSRDNATL QATLHAARDT LASVFRLLHS LDQAKEELER LAASLDGART PLLQRMQTFS PAGSKLRLVE AAEAHAQQLG QLALNLSSII LDVNQDRLTQ RAIEASNAYS RILQAVQAAE DAAGQALQQA DHTWATVVRQ GLVDRAQQLL ANSTALEEAM LQEQQRLGLV WAALQGARTQ LRDVRAKKDQ LEAHIQAAQA MLAMDTDETS KKIAHAKAVA AEAQDTATRV QSQLQAMQEN VERWQGQYEG LRGQDLGQAV LDAGHSVSTL EKTLPQLLAK LSILENRGVH NASLALSASI GRVRELIAQA RGAASKVKVP MKFNGRSGVQ LRTPRDLADL AAYTALKFYL QGPEPEPGQG TEDRFVMYMG SRQATGDYMG VSLRDKKVHW VYQLGEAGPA VLSIDEDIGE QFAAVSLDRT LQFGHMSVTV ERQMIQETKG DTVAPGAEGL LNLRPDDFVF YVGGYPSTFT PPPLLRFPGY RGCIEMDTLN EEVVSLYNFE RTFQLDTAVD RPCARSKSTG DPWLTDGSYL DGTGFARISF DSQISTTKRF EQELRLVSYS GVLFFLKQQS QFLCLAVQEG SLVLLYDFGA GLKKAVPLQP PPPLTSASKA IQVFLLGGSR KRVLVRVERA TVYSVEQDND LELADAYYLG GVPPDQLPPS LRRLFPTGGS VRGCVKGIKA LGKYVDLKRL NTTGVSAGCT ADLLVGRAMT FHGHGFLRLA LSNVAPLTGN VYSGFGFHSA QDSALLYYRA SPDGLCQVSL QQGRVSLQLL RTEVKTQAGF ADGAPHYVAF YSNATGVWLY VDDQLQQMKP HRGPPPELQP QPEGPPRLLL GGLPESGTIY NFSGCISNVF VQRLLGPQRV FDLQQNLGSV NVSTGCAPAL QAQTPGLGPR GLQATARKVG TPGASRRSRQ PARHPACMLP PHLRTTRDSY QFGGSLSSHL EFVGILARHR NWPSLSMHVL PRSSRGLLLF TARLRPGSPS LALFLSNGHF VAQMEGLGTR LRAQSRQRSR PGRWHKVSVR WEKNRILLVT DGARAWSQEG PHRQHQGAEH PQPHTLFVGG LPASSHSSKL PVTVGFSGCV KRLRLHGRPL GAPTRMAGVT PCILGPLEAG LFFPGSGGVI TLDLPGATLP DVGLELEVRP LAVTGLIFHL GQARTPPYLQ LQVTEKQVLL RADDGAGEFS TSVTRPSVLC DGQWHRLAVM KSGNVLRLEV DAQSNHTVGP LLAAAAGAPA PLYLGGLPEP MAVQPWPPAY CGCMRRLAVN RSPVAMTRSV EVHGAVGASG CPAA (SEQ ID NO:2)

[0137] In some embodiments, the laminin moiety comprises an amino acid sequence having at least 76% sequence identity to the mature human laminin alpha 5 (α5 or LAMA5) X2 variant polypeptide chain or fragment thereof. The mature amino acid sequence of the human laminin alpha 5 chain X2 variant represented by SEQ ID NO:2 is set forth below. REEAG GGFSLHPPYF NLAEGARIAA SATCGEEAPA RGSPRPTEDL YCKLVGGPVA GGDPNQTIRG QYCDICTAAN SNKAHPASNA IDGTERWWQS PPLSRGLEYN EVNVTLDLGQ VFHVAYVLIK FANSPRPDLW VLERSMDFGR TYQP WQFFAS SKRDCLERFG PQTLERITRD DAAICTTEYS RIVPLENGEI VVSLVNGRPG AMNFSYSPLL REFTKATNVR LRFLRTNTLLGHLMGKALRD PTVTRRYYYS IKDISIGGRC VCHGHADACD AKDPTDPFRL QCTCQHNTCG GTCDRCCPGF NQQPWKPATA NSANECQSCN CYGHATDCYY DPEVDRRRAS QSLDGTYQGG GVCIDCQHHT TGVNCERCLP GFYRSPNHPL DSPHVCRRCN CESDFTDGTC EDLTGRCYCR PNFSGERCDV CAEGFTGFPS CYPTPSSSND TREQVLPAGQ IVNCDCSAAG TQGNACRKDP RVGRCLCKPN FQGTHCELCA PGFYGPGCQP CQCSSPGVAD DRCDPDTGQC RCRVGFEGAT CDRCAPGYFH FPLCQLCGCS PAGTLPEGCD EAGRCLCQPE FAGPHCDRCR PGYHGFPNCQ ACTCDPRGAL DQLCGAGGLC RCRPGYTGTA CQECSPGFHG FPSCVPGSCH PAGLAPVDPA LPEAQVPCMC RAHVEGPSCD RCKPGFWGLS PSNPEGCTRC SCDLRGTLGG VAECQPGTGQ CFCKPHVCGQ ACASCKDGFF GLDQADYFGC RSCRCDIGGA LGQSCEPRTG VCRCRPNTQG PTCSEPARDH YLPDLHHLRL ELEEAATPEG HAVRFGFNPL EFENFSWRGY AQMAPVQPRI VARLNLTSPD LFWLVFRYVN RGAMSVSGRV SVREEGRSAT CANCTAQSQP VAFPPSTEPA FITVPQRGFG EPFVLNPGTW ALRVEAEGVL LDYVVLLPSA YYEAALLQLR VTEACTYRPS AQQSGDNCLL YTHLPLDGFP SAAGLEALCR QDNSLPRPCP TEQLSPSHPP LITCTGSDVD VQLQVAVPQP GRYALVVEYA NEDARQEVGV AVHTPQRAPQ QGLLSLHPCL YSTLCRGTAR DTQDHLAVFH LDSEASVRLT AEQARFFLHG VTLVPIEEFS PEFVEPRVSC ISSHGAFGPN SAACLPSRFP KPPQPIILRD CQVIPLPPGL PLTHAQDLTP AMSPAGPRPR PPTAVDPDAE PTLLREPQAT VVFTTHVPTL GRYAFLLHGY QPAHPTFPVE VLINAGRVWQ GHANASFCPH GYGCRTLVVC EGQALLDVTH SELTVTVRVP KGRWLWLDYV LVVPENVYSF GYLREEPLDK SYDFISHCAA QGYHISPSSS SLFCRNAAAS LSLFYNNGAR PCGCHEVGAT GPTCEPFGGQ CPCHAHVIGR DCSRCATGYW GFPNCRPCDC GARLCDELTG QCICPPRTIP PDCLLCQPQT FGCHPLVGCE ECNCSGPGIQ ELTDPTCDTD SGQCKCRPNV TGRRCDTCSP GFHGYPRCRP CDCHEAGTAP GVCDPLTGQC YCKENVQGPK CDQCSLGTFS LDAANPKGCT RCFCFGATER CRSSSYTRQE FVDMEGWVLL STDRQVVPHE RQPGTEMLRA DLRHVPEAVP EAFPELYWQA PPSYLGDRVS SYGGTLRYEL HSETQRGDVF VPMESRPDVV LQGNQMSITF LEPAYPTPGH VHRGQLQLVE GNFRHTETRN TVSREELMMV LASLEQLQIR ALFSQISSAV FLRRVALEVA SPAGQGALAS NVELCLCPAS YRGDSCQECA PGFYRDVKGL FLGRCVPCQC HGHSDRCLPG SGVCVDCQHN TEGAHCERCQ AGFVSSRDDP SAPCVSCPCP LSVPSNNFAE GCVLRGGRTQ CLCKPGYAGA SCERCAPGFF GNPLVLGSSC QPCDCSGNGD PNLLFSDCDP LTGACRGCLR HTTGPRCEIC APGFYGNALL PGNCTRCDCT PCGTEACDPH SGHCLCKAGV TGRRCDRCQE GHFGFDGCGG CRPCACGPAA EGSECHPQSG QCHCRPGTMG PQCRECAPGY WGLPEQGCRR CQCPGGRCDP HTGRCNCPPG LSGERCDTCS QQHQVPVPGG PVGHSIHCEV CDHCVVLLLD DLERAGALLP AIHEQLRGIN ASSMAWARLH RLNASIADLQ SQLRSPLGPR HETAQQLEVL EQQSTSLGQD ARRLGGQAVG TRDQASQLLA GTEATLGHAK TLLAAIRAVD RTLSELMSQT GHLGLANASA PSGEQLLRTL AEVERLLWEM RARDLGAPQA AAEAELAAAQ RLLARVQEQL SSLWEENQAL ATQTRDRLAQ HEAGLMDLRE ALNRAVDATR EAQELNSRNQ ERLEEALQRK QELSRDNATL QATLHAARDT LASVFRLLHS LDQAKEELER LAASLDGART PLLQRMQTFS PAGSKLRLVE AAEAHAQQLG QLALNLSSII LDVNQDRLTQ RAIEASNAYS RILQAVQAAE DAAGQALQQA DHTWATVVRQ GLVDRAQQLL ANSTALEEAM LQEQQRLGLV WAALQGARTQ LRDVRAKKDQ LEAHIQAAQA MLAMDTDETS KKIAHAKAVA AEAQDTATRV QSQLQAMQEN VERWQGQYEG LRGQDLGQAV LDAGHSVSTL EKTLPQLLAK LSILENRGVH NASLALSASI GRVRELIAQA RGAASKVKVP MKFNGRSGVQ LRTPRDLADL AAYTALKFYL QGPEPEPGQG TEDRFVMYMG SRQATGDYMG VSLRDKKVHW VYQLGEAGPA VLSIDEDIGE QFAAVSLDRT LQFGHMSVTV ERQMIQETKG DTVAPGAEGL LNLRPDDFVF YVGGYPSTFT PPPLLRFPGY RGCIEMDTLN EEVVSLYNFE RTFQLDTAVD RPCARSKSTG DPWLTDGSYL DGTGFARISF DSQISTTKRF EQELRLVSYS GVLFFLKQQS QFLCLAVQEG SLVLLYDFGA GLKKAVPLQP PPPLTSASKA IQVFLLGGSR KRVLVRVERA TVYSVEQDND LELADAYYLG GVPPDQLPPS LRRLFPTGGS VRGCVKGIKA LGKYVDLKRL NTTGVSAGCT ADLLVGRAMT FHGHGFLRLA LSNVAPLTGN VYSGFGFHSA QDSALLYYRA SPDGLCQVSL QQGRVSLQLL RTEVKTQAGF ADGAPHYVAF YSNATGVWLY VDDQLQQMKP HRGPPPELQP QPEGPPRLLL GGLPESGTIY NFSGCISNVF VQRLLGPQRV FDLQQNLGSV NVSTGCAPAL QAQTPGLGPR GLQATARKVG TPGASRRSRQ PARHPACMLP PHLRTTRDSY QFGGSLSSHL EFVGILARHR NWPSLSMHVL PRSSRGLLLF TARLRPGSPS LALFLSNGHF VAQMEGLGTR LRAQSRQRSR PGRWHKVSVR WEKNRILLVT DGARAWSQEG PHRQHQGAEH PQPHTLFVGG LPASSHSSKL PVTVGFSGCV KRLRLHGRPL GAPTRMAGVT PCILGPLEAG LFFPGSGGVI TLDLPGATLP DVGLELEVRP LAVTGLIFHL GQARTPPYLQ LQVTEKQVLL RADDGAGEFS TSVTRPSVLC DGQWHRLAVM KSGNVLRLEV DAQSNHTVGP LLAAAAGAPA PLYLGGLPEP MAVQPWPPAY CGCMRRLAVN RSPVAMTRSV EVHGAVGASG CPAA (SEQ ID NO:32)

[0138] In some embodiments, the laminin moiety comprises an amino acid sequence having at least 76% sequence identity, at least 77% sequence identity, at least 78% sequence identity, at least 79% sequence identity, at least 80% sequence identity, at least 81% sequence identity, at least 82% sequence identity, at least 83% sequence identity, at least 84% sequence identity, at least 85% sequence identity, at least 86% sequence identity, at least 87% sequence identity, at least 88% sequence identity, at least 89% sequence identity, at least 90% sequence identity at least 91% sequence identity, at least 92% sequence identity, at least 93% sequence identity, at least 94% sequence identity, at least 95% sequence identity, at least 96% sequence identity, at least 97% sequence identity, at least 98% sequence identity, at least 99% sequence identity or 100% sequence identity to the amino acid sequence of NO:32 or a fragment thereof that supports adhesion of PSCs to a substrate.

[0139] In some embodiments, the laminin moiety is a murine laminin alpha 5 chain. The full- length amino acid sequence of a representative murine laminin alpha 5 chain (corresponding to Uniprot # Q61001) is set forth below, with the signal sequence underlined. MAKRGGQLCA GSAPGALGPR SPAPRPLLLL LAGLALVGEA RTPGGDGFSL HPPYFNLAEG ARITASATCG EEAPTRSVSR PTEDLYCKLV GGPVAGGDPN QTIQGQYCDI CTAANSNKAH PVSNAIDGTE RWWQSPPLSR GLEYNEVNVT LDLGQVFHVA YVLIKFANSP RPDLWVLERS TDFGHTYQPW QFFASSKRDC LERFGPRTLE RITQDDDVIC TTEYSRIVPL ENGEIVVSLV NGRPGALNFS YSPLLRDFTK ATNIRLRFLR TNTLLGHLMG KALRDPTVTR RYYYSIKDIS IGGRCVCHGH ADVCDAKDPL DPFRLQCACQ HNTCGGSCDR CCPGFNQQPW KPATTDSANE CQSCNCHGHA YDCYYDPEVD RRNASQNQDN VYQGGGVCLD CQHHTTGINC ERCLPGFFRA PDQPLDSPHV CRPCDCESDF TDGTCEDLTG RCYCRPNFTG ELCAACAEGY TDFPHCYPLP SFPHNDTREQ VLPAGQIVNC DCNAAGTQGN ACRKDPRLGR CVCKPNFRGA HCELCAPGFH GPSCHPCQCS SPGVANSLCD PESGQCMCRT GFEGDRCDHC ALGYFHFPLC QLCGCSPAGT LPEGCDEAGR CQCRPGFDGP HCDRCLPGYH GYPDCHACAC DPRGALDQQC GVGGLCHCRP GYTGATCQEC SPGFYGFPSC IPCHCSADGS LHTTCDPTTG QCRCRPRVTG LHCDMCVPGA YNFPYCEAGS CHPAGLAPAN PALPETQAPC MCRAHVEGPS CDRCKPGYWG LSASNPEGCT RCSCDPRGTL GGVTECQGNG QCFCKAHVCG KTCAACKDGF FGLDYADYFG CRSCRCDVGG ALGQGCEPKT GACRCRPNTQ GPTCSEPAKD HYLPDLHHMR LELEEAATPE GHAVRFGFNP LEFENFSWRG YAHMMAIQPR IVARLNVTSP DLFRLVFRYV NRGSTSVNGQ ISVREEGKLS SCTNCTEQSQ PVAFPPSTEP AFVTVPQRGF GEPFVLNPGI WALLVEAEGV LLDYVVLLPS TYYEAALLQH RVTEACTYRP SALHSTENCL VYAHLPLDGF PSAAGTEALC RHDNSLPRPC PTEQLSPSHP PLATCFGSDV DIQLEMAVPQ PGQYVLVVEY VGEDSHQEMG VAVHTPQRAP QQGVLNLHPC PYSSLCRSPA RDTQHHLAIF YLDSEASIRL TAEQAHFFLH SVTLVPVEEF STEFVEPRVF CVSSHGTFNP SSAACLASRF PKPPQPIILK DCQVLPLPPD LPLTQSQELS PGAPPEGPQP RPPTAVDPNA EPTLLRHPQG TVVFTTQVPT LGRYAFLLHG YQPVHPSFPV EVLINGGRIW QGHANASFCP HGYGCRTLVL CEGQTMLDVT DNELTVTVRV PEGRWLWLDY VLIVPEDAYS SSYLQEEPLD KSYDFISHCA TQGYHISPSS SSPFCRNAAT SLSLFYNNGA LPCGCHEVGA VSPTCEPFGG QCPCRGHVIG RDCSRCATGY WGFPNCRPCD CGARLCDELT GQCICPPRTV PPDCLVCQPQ SFGCHPLVGC EECNCSGPGV QELTDPTCDM DSGQCRCRPN VAGRRCDTCA PGFYGYPSCR PCDCHEAGTM ASVCDPLTGQ CHCKENVQGS RCDQCRVGTF SLDAANPKGC TRCFCFGATE RCGNSNLARH EFVDMEGWVL LSSDRQVVPH EHRPEIELLH ADLRSVADTF SELYWQAPPS YLGDRVSSYG GTLHYELHSE TQRGDIFIPY ESRPDVVLQG NQMSIAFLEL AYPPPGQVHR GQLQLVEGNF RHLETHNPVS REELMMVLAG LEQLQIRALF SQTSSSVSLR RVVLEVASEA GRGPPASNVE LCMCPANYRG DSCQECAPGY YRDTKGLFLG RCVPCQCHGH SDRCLPGSGI CVGCQHNTEG DQCERCRPGF VSSDPSNPAS PCVSCPCPLA VPSNNFADGC VLRNGRTQCL CRPGYAGASC ERCAPGFFGN PLVLGSSCQP CDCSGNGDPN MIFSDCDPLT GACRGCLRHT TGPHCERCAP GFYGNALLPG NCTRCDCSPC GTETCDPQSGRCLCKAGVTG QRCDRCLEGY FGFEQCQGCR PCACGPAAKG SECHPQSGQC HCQPGTTGPQ CLECAPGYWG LPEKGCRRCQ CPRGHCDPHT GHCTCPPGLS GERCDTCSQQ HQVPVPGKPG GHGIHCEVCD HCVVLLLDDL ERAGALLPAI REQLQGINAS SAAWARLHRL NASIADLQSK LRSPPGPRYQ AAQQLQTLEQ QSISLQQDTE RLGSQATGVQ GQAGQLLDTT ESTLGRAQKL LESVRAVGRA LNELASRMGQ GSPGDALVPS GEQLRWALAE VERLLWDMRT RDLGAQGAVA EAELAEAQRL MARVQEQLTS FWEENQSLAT HIRDQLAQYE SGLMDLREAL NQAVNTTREA EELNSRNQER LKEALQWKQE LSQDNATLKA TLQAASLILG HVSELLQGID QAKEDLEHLA ASLDGAWTPL LKRMQAFSPA SSKVDLVEAA EAHAQKLNQL AINLSGIILG INQDRFIQRA VEASNAYSSI LQAVQAAEDA AGQALRQASR TWEMVVQRGL AAGARQLLAN SSALEETILG HQGRLGLAQG RLQAAGIQLH NVWARKNQLA AQIQEAQAML AMDTSETSEK IAHAKAVAAE ALSTATHVQS QLQGMQKNVE RWQSQLGGLQ GQDLSQVERD ASSSVSTLEK TLPQLLAKLS RLENRGVHNA SLALSANIGR VRKLIAQARS AASKVKVSMK FNGRSGVRLR TPRDLADLAA YTALKFHIQS PVPAPEPGKN TGDHFVLYMG SRQATGDYMG VSLRNQKVHW VYRLGKAGPT TLSIDENIGE QFAAVSIDRT LQFGHMSVTV EKQMVHEIKG DTVAPGSEGL LNLHPDDFVF YVGGYPSNFT PPEPLRFPGY LGCIEMETLN EEVVSLYNFE QTFMLDTAVD KPCARSKATG DPWLTDGSYL DGSGFARISF EKQFSNTKRF DQELRLVSYN GIIFFLKQES QFLCLAVQEG TLVLFYDFGS GLKKADPLQP PQALTAASKA IQVFLLAGNR KRVLVRVERA TVFSVDQDNM LEMADAYYLG GVPPEQLPLS LRQLFPSGGS VRGCIKGIKA LGKYVDLKRL NTTGISFGCT ADLLVGRTMT FHGHGFLPLA LPDVAPITEV VYSGFGFRGT QDNNLLYYRT SPDGPYQVSL REGHVTLRFM NQEVETQRVF ADGAPHYVAF YSNVTGVWLY VDDQLQLVKS HERTTPMLQL QPEEPSRLLL GGLPVSGTFH NFSGCISNVF VQRLRGPQRV FDLHQNMGSV NVSVGCTPAQ LIETSRATAQ KVSRRSRQPS QDLACTTPWL PGTIQDAYQF GGPLPSYLQF VGISPSHRNR LHLSMLVRPH AASQGLLLST APMSGRSPSL VLFLNHGHFV AQTEGPGPRL QVQSRQHSRA GQWHRVSVRW GMQQIQLVVD GSQTWSQKAL HHRVPRAERP QPYTLSVGGL PASSYSSKLP VSVGFSGCLK KLQLDKRPLR TPTQMVGVTP CVSGPLEDGL FFPGSEGVVT LELPKAKMPY VSLELEMRPL AAAGLIFHLG QALATPYMQL KVLTEQVLLQ ANDGAGEFST WVTYPKLCDG RWHRVAVIMG RDTLRLEVDT QSNHTTGRLP ESLAGSPALL HLGSLPKSST ARPELPAYRG CLRKLLINGA PVNVTASVQI QGAVGMRGCP SGTLALSKQG KALTQRQAKP SVSPLLWH (SEQ ID NO:3)

[0140] In some embodiments, the laminin moiety comprises an amino acid sequence having at least 90% sequence identity to the mature murine laminin alpha 5 (α5 or LAMA5) polypeptide chain or fragment thereof. The mature amino acid sequence of the murine laminin alpha 5 chain represented by SEQ ID NO:3 is set forth below. RTPGGDGFSL HPPYFNLAEG ARITASATCG EEAPTRSVSR PTEDLYCKLV GGPVAGGDPN QTIQGQYCDI CTAANSNKAH PVSNAIDGTE RWWQSPPLSR GLEYNEVNVT LDLGQVFHVA YVLIKFANSP RPDLWVLERS TDFGHTYQPW QFFASSKRDC LERFGPRTLE RITQDDDVIC TTEYSRIVPL ENGEIVVSLV NGRPGALNFS YSPLLRDFTK ATNIRLRFLR TNTLLGHLMG KALRDPTVTR RYYYSIKDIS IGGRCVCHGH ADVCDAKDPL DPFRLQCACQ HNTCGGSCDR CCPGFNQQPW KPATTDSANE CQSCNCHGHA YDCYYDPEVD RRNASQNQDN VYQGGGVCLD CQHHTTGINC ERCLPGFFRA PDQPLDSPHV CRPCDCESDF TDGTCEDLTG RCYCRPNFTG ELCAACAEGY TDFPHCYPLP SFPHNDTREQ VLPAGQIVNC DCNAAGTQGN ACRKDPRLGR CVCKPNFRGA HCELCAPGFH GPSCHPCQCS SPGVANSLCD PESGQCMCRT GFEGDRCDHC ALGYFHFPLC QLCGCSPAGT LPEGCDEAGR CQCRPGFDGP HCDRCLPGYH GYPDCHACAC DPRGALDQQC GVGGLCHCRP GYTGATCQEC SPGFYGFPSC IPCHCSADGS LHTTCDPTTG QCRCRPRVTG LHCDMCVPGA YNFPYCEAGS CHPAGLAPAN PALPETQAPC MCRAHVEGPS CDRCKPGYWG LSASNPEGCT RCSCDPRGTL GGVTECQGNG QCFCKAHVCG KTCAACKDGF FGLDYADYFG CRSCRCDVGG ALGQGCEPKT GACRCRPNTQ GPTCSEPAKD HYLPDLHHMR LELEEAATPE GHAVRFGFNP LEFENFSWRG YAHMMAIQPR IVARLNVTSP DLFRLVFRYV NRGSTSVNGQ ISVREEGKLS SCTNCTEQSQ PVAFPPSTEP AFVTVPQRGF GEPFVLNPGI WALLVEAEGV LLDYVVLLPS TYYEAALLQH RVTEACTYRP SALHSTENCL VYAHLPLDGF PSAAGTEALC RHDNSLPRPC PTEQLSPSHP PLATCFGSDV DIQLEMAVPQ PGQYVLVVEY VGEDSHQEMG VAVHTPQRAP QQGVLNLHPC PYSSLCRSPA RDTQHHLAIF YLDSEASIRL TAEQAHFFLH SVTLVPVEEFSTEFVEPRVF CVSSHGTFNP SSAACLASRF PKPPQPIILK DCQVLPLPPD LPLTQSQELS PGAPPEGPQP RPPTAVDPNA EPTLLRHPQG TVVFTTQVPT LGRYAFLLHG YQPVHPSFPV EVLINGGRIW QGHANASFCP HGYGCRTLVL CEGQTMLDVT DNELTVTVRV PEGRWLWLDY VLIVPEDAYS SSYLQEEPLD KSYDFISHCA TQGYHISPSS SSPFCRNAAT SLSLFYNNGA LPCGCHEVGA VSPTCEPFGG QCPCRGHVIG RDCSRCATGY WGFPNCRPCD CGARLCDELT GQCICPPRTV PPDCLVCQPQ SFGCHPLVGC EECNCSGPGV QELTDPTCDM DSGQCRCRPN VAGRRCDTCA PGFYGYPSCR PCDCHEAGTM ASVCDPLTGQ CHCKENVQGS RCDQCRVGTF SLDAANPKGC TRCFCFGATE RCGNSNLARH EFVDMEGWVL LSSDRQVVPH EHRPEIELLH ADLRSVADTF SELYWQAPPS YLGDRVSSYG GTLHYELHSE TQRGDIFIPY ESRPDVVLQG NQMSIAFLEL AYPPPGQVHR GQLQLVEGNF RHLETHNPVS REELMMVLAG LEQLQIRALF SQTSSSVSLR RVVLEVASEA GRGPPASNVE LCMCPANYRG DSCQECAPGY YRDTKGLFLG RCVPCQCHGH SDRCLPGSGI CVGCQHNTEG DQCERCRPGF VSSDPSNPAS PCVSCPCPLA VPSNNFADGC VLRNGRTQCL CRPGYAGASC ERCAPGFFGN PLVLGSSCQP CDCSGNGDPN MIFSDCDPLT GACRGCLRHT TGPHCERCAP GFYGNALLPG NCTRCDCSPC GTETCDPQSG RCLCKAGVTG QRCDRCLEGY FGFEQCQGCR PCACGPAAKG SECHPQSGQC HCQPGTTGPQ CLECAPGYWG LPEKGCRRCQ CPRGHCDPHT GHCTCPPGLS GERCDTCSQQ HQVPVPGKPG GHGIHCEVCD HCVVLLLDDL ERAGALLPAI REQLQGINAS SAAWARLHRL NASIADLQSK LRSPPGPRYQ AAQQLQTLEQ QSISLQQDTE RLGSQATGVQ GQAGQLLDTT ESTLGRAQKL LESVRAVGRA LNELASRMGQ GSPGDALVPS GEQLRWALAE VERLLWDMRT RDLGAQGAVA EAELAEAQRL MARVQEQLTS FWEENQSLAT HIRDQLAQYE SGLMDLREAL NQAVNTTREA EELNSRNQER LKEALQWKQE LSQDNATLKA TLQAASLILG HVSELLQGID QAKEDLEHLA ASLDGAWTPL LKRMQAFSPA SSKVDLVEAA EAHAQKLNQL AINLSGIILG INQDRFIQRA VEASNAYSSI LQAVQAAEDA AGQALRQASR TWEMVVQRGL AAGARQLLAN SSALEETILG HQGRLGLAQG RLQAAGIQLH NVWARKNQLA AQIQEAQAML AMDTSETSEK IAHAKAVAAE ALSTATHVQS QLQGMQKNVE RWQSQLGGLQ GQDLSQVERD ASSSVSTLEK TLPQLLAKLS RLENRGVHNA SLALSANIGR VRKLIAQARS AASKVKVSMK FNGRSGVRLR TPRDLADLAA YTALKFHIQS PVPAPEPGKN TGDHFVLYMG SRQATGDYMG VSLRNQKVHW VYRLGKAGPT TLSIDENIGE QFAAVSIDRT LQFGHMSVTV EKQMVHEIKG DTVAPGSEGL LNLHPDDFVF YVGGYPSNFT PPEPLRFPGY LGCIEMETLN EEVVSLYNFE QTFMLDTAVD KPCARSKATG DPWLTDGSYL DGSGFARISF EKQFSNTKRF DQELRLVSYN GIIFFLKQES QFLCLAVQEG TLVLFYDFGS GLKKADPLQP PQALTAASKA IQVFLLAGNR KRVLVRVERA TVFSVDQDNM LEMADAYYLG GVPPEQLPLS LRQLFPSGGS VRGCIKGIKA LGKYVDLKRL NTTGISFGCT ADLLVGRTMT FHGHGFLPLA LPDVAPITEV VYSGFGFRGT QDNNLLYYRT SPDGPYQVSL REGHVTLRFM NQEVETQRVF ADGAPHYVAF YSNVTGVWLY VDDQLQLVKS HERTTPMLQL QPEEPSRLLL GGLPVSGTFH NFSGCISNVF VQRLRGPQRV FDLHQNMGSV NVSVGCTPAQ LIETSRATAQ KVSRRSRQPS QDLACTTPWL PGTIQDAYQF GGPLPSYLQF VGISPSHRNR LHLSMLVRPH AASQGLLLST APMSGRSPSL VLFLNHGHFV AQTEGPGPRL QVQSRQHSRA GQWHRVSVRW GMQQIQLVVD GSQTWSQKAL HHRVPRAERP QPYTLSVGGL PASSYSSKLP VSVGFSGCLK KLQLDKRPLR TPTQMVGVTP CVSGPLEDGL FFPGSEGVVT LELPKAKMPY VSLELEMRPL AAAGLIFHLG QALATPYMQL KVLTEQVLLQ ANDGAGEFST WVTYPKLCDG RWHRVAVIMG RDTLRLEVDT QSNHTTGRLP ESLAGSPALL HLGSLPKSST ARPELPAYRG CLRKLLINGA PVNVTASVQI QGAVGMRGCP SGTLALSKQG KALTQRQAKP SVSPLLWH (SEQ ID NO:33)

[0141] In some embodiments, the laminin moiety comprises an amino acid sequence having at least 76% sequence identity, at least 77% sequence identity, at least 78% sequence identity, at least 79% sequence identity, at least 80% sequence identity, at least 81% sequence identity, at least 82% sequence identity, at least 83% sequence identity, at least 84% sequence identity, at least 85% sequence identity, at least 86% sequence identity, at least 87% sequence identity, at least 88% sequence identity, at least 89% sequence identity, at least 90% sequence identity at least 91% sequence identity, at least 92% sequence identity, at least 93% sequence identity, at least 94% sequence identity, at least 95% sequence identity, at least 96% sequence identity, at least 97% sequence identity, at least 98% sequence identity, at least 99% sequence identity or100% sequence identity to the amino acid sequence of SEQ ID NO:33 or a fragment thereof that supports adhesion of PSCs to a substrate.

[0142] In some embodiments, the laminin moiety comprises a laminin alpha 5 polypeptide fragment of at least 150 consecutive amino acids from amino acid 2500 to the C-terminus of any one of SEQ ID NOS: 1-3 or an amino acid sequence that has at least 79% sequence identity to at least 150 consecutive amino acids from amino acid 2500 to the C-terminus of any one of amino acid sequences of SEQ ID NOS: 1-3.

[0143] In some embodiments, the laminin moiety comprises a laminin beta 1 (β1 or LAMB1) polypeptide or fragment thereof. The full-length amino acid sequence of a representative human laminin beta 1 chain is set forth below, with the signal sequence underlined. MGLLQLLAFSFLALCRARVRAQEPEFSYGCAEGSCYPATGDLLIGRAQKLSVTSTCGLHKPEPYCIVSHL QEDKKCFICNSQDPYHETLNPDSHLIENVVTTFAPNRLKIWWQSENGVENVTIQLDLEAEFHFTHLIMTF KTFRPAAMLIERSSDFGKTWGVYRYFAYDCEASFPGISTGPMKKVDDIICDSRYSDIEPSTEGEVIFRAL DPAFKIEDPYSPRIQNLLKITNLRIKFVKLHTLGDNLLDSRMEIREKYYYAVYDMVVRGNCFCYGHASEC APVDGFNEEVEGMVHGHCMCRHNTKGLNCELCMDFYHDLPWRPAEGRNSNACKKCNCNEHSISCHFDMAV YLATGNVSGGVCDDCQHNTMGRNCEQCKPFYYQHPERDIRDPNFCERCTCDPAGSQNEGICDSYTDFSTG LIAGQCRCKLNVEGEHCDVCKEGFYDLSSEDPFGCKSCACNPLGTIPGGNPCDSETGHCYCKRLVTGQHC DQCLPEHWGLSNDLDGCRPCDCDLGGALNNSCFAESGQCSCRPHMIGRQCNEVEPGYYFATLDHYLYEAE EANLGPGVSIVERQYIQDRIPSWTGAGFVRVPEGAYLEFFIDNIPYSMEYDILIRYEPQLPDHWEKAVIT VQRPGRIPTSSRCGNTIPDDDNQVVSLSPGSRYVVLPRPVCFEKGTNYTVRLELPQYTSSDSDVESPYTL IDSLVLMPYCKSLDIFTVGGSGDGVVTNSAWETFQRYRCLENSRSVVKTPMTDVCRNIIFSISALLHQTG LACECDPQGSLSSVCDPNGGQCQCRPNVVGRTCNRCAPGTFGFGPSGCKPCECHLQGSVNAFCNPVTGQC HCFQGVYARQCDRCLPGHWGFPSCQPCQCNGHADDCDPVTGECLNCQDYTMGHNCERCLAGYYGDPIIGS GDHCRPCPCPDGPDSGRQFARSCYQDPVTLQLACVCDPGYIGSRCDDCASGYFGNPSEVGGSCQPCQCHN NIDTTDPEACDKETGRCLKCLYHTEGEHCQFCRFGYYGDALQQDCRKCVCNYLGTVQEHCNGSDCQCDKA TGQCLCLPNVIGQNCDRCAPNTWQLASGTGCDPCNCNAAHSFGPSCNEFTGQCQCMPGFGGRTCSECQEL FWGDPDVECRACDCDPRGIETPQCDQSTGQCVCVEGVEGPRCDKCTRGYSGVFPDCTPCHQCFALWDVII AELTNRTHRFLEKAKALKISGVIGPYRETVDSVERKVSEIKDILAQSPAAEPLKNIGNLFEEAEKLIKDV TEMMAQVEVKLSDTTSQSNSTAKELDSLQTEAESLDNTVKELAEQLEFIKNSDIRGALDSITKYFQMSLE AEERVNASTTEPNSTVEQSALMRDRVEDVMMERESQFKEKQEEQARLLDELAGKLQSLDLSAAAEMTCGT PPGASCSETECGGPNCRTDEGERKCGGPGCGGLVTVAHNAWQKAMDLDQDVLSALAEVEQLSKMVSEAKL RADEAKQSAEDILLKTNATKEKMDKSNEELRNLIKQIRNFLTQDSADLDSIEAVANEVLKMEMPSTPQQL QNLTEDIRERVESLSQVEVILQHSAADIARAEMLLEEAKRASKSATDVKVTADMVKEALEEAEKAQVAAE KAIKQADEDIQGTQNLLTSIESETAASEETLFNASQRISELERNVEELKRKAAQNSGEAEYIEKVVYTVK QSAEDVKKTLDGELDEKYKKVENLIAKKTEESADARRKAEMLQNEAKTLLAQANSKLQLLKDLERKYEDN QRYLEDKAQELARLEGEVRSLLKDISQKVAVYSTCL (SEQ ID NO:13)

[0144] In some embodiments, the laminin moiety comprises an amino acid sequence having at least 90% sequence identity to the mature human laminin beta 1 polypeptide chain or fragment thereof. The mature amino acid sequence of the human laminin beta 1 chain represented by SEQ ID NO:13 is set forth below. QEPEFSYGCAEGSCYPATGDLLIGRAQKLSVTSTCGLHKPEPYCIVSHLQEDKKCFICNSQDPYHETLNP DSHLIENVVTTFAPNRLKIWWQSENGVENVTIQLDLEAEFHFTHLIMTFKTFRPAAMLIERSSDFGKTWG VYRYFAYDCEASFPGISTGPMKKVDDIICDSRYSDIEPSTEGEVIFRALDPAFKIEDPYSPRIQNLLKIT NLRIKFVKLHTLGDNLLDSRMEIREKYYYAVYDMVVRGNCFCYGHASECAPVDGFNEEVEGMVHGHCMCR HNTKGLNCELCMDFYHDLPWRPAEGRNSNACKKCNCNEHSISCHFDMAVYLATGNVSGGVCDDCQHNTMG RNCEQCKPFYYQHPERDIRDPNFCERCTCDPAGSQNEGICDSYTDFSTGLIAGQCRCKLNVEGEHCDVCKEGFYDLSSEDPFGCKSCACNPLGTIPGGNPCDSETGHCYCKRLVTGQHCDQCLPEHWGLSNDLDGCRPCD CDLGGALNNSCFAESGQCSCRPHMIGRQCNEVEPGYYFATLDHYLYEAEEANLGPGVSIVERQYIQDRIP SWTGAGFVRVPEGAYLEFFIDNIPYSMEYDILIRYEPQLPDHWEKAVITVQRPGRIPTSSRCGNTIPDDD NQVVSLSPGSRYVVLPRPVCFEKGTNYTVRLELPQYTSSDSDVESPYTLIDSLVLMPYCKSLDIFTVGGS GDGVVTNSAWETFQRYRCLENSRSVVKTPMTDVCRNIIFSISALLHQTGLACECDPQGSLSSVCDPNGGQ CQCRPNVVGRTCNRCAPGTFGFGPSGCKPCECHLQGSVNAFCNPVTGQCHCFQGVYARQCDRCLPGHWGF PSCQPCQCNGHADDCDPVTGECLNCQDYTMGHNCERCLAGYYGDPIIGSGDHCRPCPCPDGPDSGRQFAR SCYQDPVTLQLACVCDPGYIGSRCDDCASGYFGNPSEVGGSCQPCQCHNNIDTTDPEACDKETGRCLKCL YHTEGEHCQFCRFGYYGDALQQDCRKCVCNYLGTVQEHCNGSDCQCDKATGQCLCLPNVIGQNCDRCAPN TWQLASGTGCDPCNCNAAHSFGPSCNEFTGQCQCMPGFGGRTCSECQELFWGDPDVECRACDCDPRGIET PQCDQSTGQCVCVEGVEGPRCDKCTRGYSGVFPDCTPCHQCFALWDVIIAELTNRTHRFLEKAKALKISG VIGPYRETVDSVERKVSEIKDILAQSPAAEPLKNIGNLFEEAEKLIKDVTEMMAQVEVKLSDTTSQSNST AKELDSLQTEAESLDNTVKELAEQLEFIKNSDIRGALDSITKYFQMSLEAEERVNASTTEPNSTVEQSAL MRDRVEDVMMERESQFKEKQEEQARLLDELAGKLQSLDLSAAAEMTCGTPPGASCSETECGGPNCRTDEG ERKCGGPGCGGLVTVAHNAWQKAMDLDQDVLSALAEVEQLSKMVSEAKLRADEAKQSAEDILLKTNATKE KMDKSNEELRNLIKQIRNFLTQDSADLDSIEAVANEVLKMEMPSTPQQLQNLTEDIRERVESLSQVEVIL QHSAADIARAEMLLEEAKRASKSATDVKVTADMVKEALEEAEKAQVAAEKAIKQADEDIQGTQNLLTSIE SETAASEETLFNASQRISELERNVEELKRKAAQNSGEAEYIEKVVYTVKQSAEDVKKTLDGELDEKYKKV ENLIAKKTEESADARRKAEMLQNEAKTLLAQANSKLQLLKDLERKYEDNQRYLEDKAQELARLEGEVRSL LKDISQKVAVYSTCL (SEQ ID NO:34)

[0145] In some embodiments, the laminin moiety comprises an amino acid sequence having at least 76% sequence identity, at least 77% sequence identity, at least 78% sequence identity, at least 79% sequence identity, at least 80% sequence identity, at least 81% sequence identity, at least 82% sequence identity, at least 83% sequence identity, at least 84% sequence identity, at least 85% sequence identity, at least 86% sequence identity, at least 87% sequence identity, at least 88% sequence identity, at least 89% sequence identity, at least 90% sequence identity at least 91% sequence identity, at least 92% sequence identity, at least 93% sequence identity, at least 94% sequence identity, at least 95% sequence identity, at least 96% sequence identity, at least 97% sequence identity, at least 98% sequence identity, at least 99% sequence identity or 100% sequence identity to the amino acid sequence of SEQ ID NO:34 or a fragment thereof that supports adhesion of PSCs to a substrate.

[0146] In some embodiments, the laminin moiety comprises a murine laminin beta 1 (β1 or LAMB1) polypeptide or fragment thereof. The full-length amino acid sequence of a representative murine laminin beta 1 chain (corresponding to UniProt #P02469) is set forth below, with the signal sequence underlined. MGLLQVFAFGVLALWGTRVCAQEPEFSYGCAEGSCYPATGDLLIGRAQKLSVTSTCGLHKPEPYCIVSHL QEDKKCFICDSRDPYHETLNPDSHLIENVVTTFAPNRLKIWWQSENGVENVTIQLDLEAEFHFTHLIMTF KTFRPAAMLIERSSDFGKAWGVYRYFAYDCESSFPGISTGPMKKVDDIICDSRYSDIEPSTEGEVIFRAL DPAFKIEDPYSPRIQNLLKITNLRIKFVKLHTLGDNLLDSRMEIREKYYYAVYDMVVRGNCFCYGHASEC APVDGVNEEVEGMVHGHCMCRHNTKGLNCELCMDFYHDLPWRPAEGRNSNACKKCNCNEHSSSCHFDMAV FLATGNVSGGVCDNCQHNTMGRNCEQCKPFYFQHPERDIRDPNLCEPCTCDPAGSENGGICDGYTDFSVG LIAGQCRCKLHVEGERCDVCKEGFYDLSAEDPYGCKSCACNPLGTIPGGNPCDSETGYCYCKRLVTGQRC DQCLPQHWGLSNDLDGCRPCDCDLGGALNNSCSEDSGQCSCLPHMIGRQCNEVESGYYFTTLDHYIYEAE EANLGPGVIVVERQYIQDRIPSWTGPGFVRVPEGAYLEFFIDNIPYSMEYEILIRYEPQLPDHWEKAVIT VQRPGKIPASSRCGNTVPDDDNQVVSLSPGSRYVVLPRPVCFEKGMNYTVRLELPQYTASGSDVESPYTF IDSLVLMPYCKSLDIFTVGGSGDGEVTNSAWETFQRYRCLENSRSVVKTPMTDVCRNIIFSISALIHQTG LACECDPQGSLSSVCDPNGGQCQCRPNVVGRTCNRCAPGTFGFGPNGCKPCDCHLQGSASAFCDAITGQC HCFQGIYARQCDRCLPGYWGFPSCQPCQCNGHALDCDTVTGECLSCQDYTTGHNCERCLAGYYGDPIIGSGDHCRPCPCPDGPDSGRQFARSCYQDPVTLQLACVCDPGYIGSRCDDCASGFFGNPSDFGGSCQPCQCHH NIDTTDPEACDKETGRCLKCLYHTEGDHCQLCQYGYYGDALRQDCRKCVCNYLGTVKEHCNGSDCHCDKA TGQCSCLPNVIGQNCDRCAPNTWQLASGTGCGPCNCNAAHSFGPSCNEFTGQCQCMPGFGGRTCSECQEL FWGDPDVECRACDCDPRGIETPQCDQSTGQCVCVEGVEGPRCDKCTRGYSGVFPDCTPCHQCFALWDAII GELTNRTHKFLEKAKALKISGVIGPYRETVDSVEKKVNEIKDILAQSPAAEPLKNIGILFEEAEKLTKDV TEKMAQVEVKLTDTASQSNSTAGELGALQAEAESLDKTVKELAEQLEFIKNSDIQGALDSITKYFQMSLE AEKRVNASTTDPNSTVEQSALTRDRVEDLMLERESPFKEQQEEQARLLDELAGKLQSLDLSAVAQMTCGT PPGADCSESECGGPNCRTDEGEKKCGGPGCGGLVTVAHSAWQKAMDFDRDVLSALAEVEQLSKMVSEAKV RADEAKQNAQDVLLKTNATKEKVDKSNEDLRNLIKQIRNFLTEDSADLDSIEAVANEVLKMEMPSTPQQL QNLTEDIRERVETLSQVEVILQQSAADIARAELLLEEAKRASKSATDVKVTADMVKEALEEAEKAQVAAE KAIKQADEDIQGTQNLLTSIESETAASEETLTNASQRISKLERNVEELKRKAAQNSGEAEYIEKVVYSVK QNADDVKKTLDGELDEKYKKVESLIAQKTEESADARRKAELLQNEAKTLLAQANSKLQLLEDLERKYEDN QKYLEDKAQELVRLEGEVRSLLKDISEKVAVYSTCL(SEQ ID NO:14)

[0147] In some embodiments, the laminin moiety comprises an amino acid sequence having at least 76% sequence identity to the mature murine laminin beta 1 polypeptide chain or fragment thereof. The mature amino acid sequence of the murine laminin beta 1 chain represented by SEQ ID NO:14 is set forth below. QEPEFSYGCAEGSCYPATGDLLIGRAQKLSVTSTCGLHKPEPYCIVSHLQEDKKCFICDSRDPYHETLNP DSHLIENVVTTFAPNRLKIWWQSENGVENVTIQLDLEAEFHFTHLIMTFKTFRPAAMLIERSSDFGKAWG VYRYFAYDCESSFPGISTGPMKKVDDIICDSRYSDIEPSTEGEVIFRALDPAFKIEDPYSPRIQNLLKIT NLRIKFVKLHTLGDNLLDSRMEIREKYYYAVYDMVVRGNCFCYGHASECAPVDGVNEEVEGMVHGHCMCR HNTKGLNCELCMDFYHDLPWRPAEGRNSNACKKCNCNEHSSSCHFDMAVFLATGNVSGGVCDNCQHNTMG RNCEQCKPFYFQHPERDIRDPNLCEPCTCDPAGSENGGICDGYTDFSVGLIAGQCRCKLHVEGERCDVCK EGFYDLSAEDPYGCKSCACNPLGTIPGGNPCDSETGYCYCKRLVTGQRCDQCLPQHWGLSNDLDGCRPCD CDLGGALNNSCSEDSGQCSCLPHMIGRQCNEVESGYYFTTLDHYIYEAEEANLGPGVIVVERQYIQDRIP SWTGPGFVRVPEGAYLEFFIDNIPYSMEYEILIRYEPQLPDHWEKAVITVQRPGKIPASSRCGNTVPDDD NQVVSLSPGSRYVVLPRPVCFEKGMNYTVRLELPQYTASGSDVESPYTFIDSLVLMPYCKSLDIFTVGGS GDGEVTNSAWETFQRYRCLENSRSVVKTPMTDVCRNIIFSISALIHQTGLACECDPQGSLSSVCDPNGGQ CQCRPNVVGRTCNRCAPGTFGFGPNGCKPCDCHLQGSASAFCDAITGQCHCFQGIYARQCDRCLPGYWGF PSCQPCQCNGHALDCDTVTGECLSCQDYTTGHNCERCLAGYYGDPIIGSGDHCRPCPCPDGPDSGRQFAR SCYQDPVTLQLACVCDPGYIGSRCDDCASGFFGNPSDFGGSCQPCQCHHNIDTTDPEACDKETGRCLKCL YHTEGDHCQLCQYGYYGDALRQDCRKCVCNYLGTVKEHCNGSDCHCDKATGQCSCLPNVIGQNCDRCAPN TWQLASGTGCGPCNCNAAHSFGPSCNEFTGQCQCMPGFGGRTCSECQELFWGDPDVECRACDCDPRGIET PQCDQSTGQCVCVEGVEGPRCDKCTRGYSGVFPDCTPCHQCFALWDAIIGELTNRTHKFLEKAKALKISG VIGPYRETVDSVEKKVNEIKDILAQSPAAEPLKNIGILFEEAEKLTKDVTEKMAQVEVKLTDTASQSNST AGELGALQAEAESLDKTVKELAEQLEFIKNSDIQGALDSITKYFQMSLEAEKRVNASTTDPNSTVEQSAL TRDRVEDLMLERESPFKEQQEEQARLLDELAGKLQSLDLSAVAQMTCGTPPGADCSESECGGPNCRTDEG EKKCGGPGCGGLVTVAHSAWQKAMDFDRDVLSALAEVEQLSKMVSEAKVRADEAKQNAQDVLLKTNATKE KVDKSNEDLRNLIKQIRNFLTEDSADLDSIEAVANEVLKMEMPSTPQQLQNLTEDIRERVETLSQVEVIL QQSAADIARAELLLEEAKRASKSATDVKVTADMVKEALEEAEKAQVAAEKAIKQADEDIQGTQNLLTSIE SETAASEETLTNASQRISKLERNVEELKRKAAQNSGEAEYIEKVVYSVKQNADDVKKTLDGELDEKYKKV ESLIAQKTEESADARRKAELLQNEAKTLLAQANSKLQLLEDLERKYEDNQKYLEDKAQELVRLEGEVRSL LKDISEKVAVYSTCL (SEQ ID NO:35)

[0148] In some embodiments, the laminin moiety comprises an amino acid sequence having at least 76% sequence identity, at least 77% sequence identity, at least 78% sequence identity, at least 79% sequence identity, at least 80% sequence identity, at least 81% sequence identity, at least 82% sequence identity, at least 83% sequence identity, at least 84% sequence identity, at least 85% sequence identity, at least 86% sequence identity, at least 87% sequence identity, at least 88% sequence identity, at least 89% sequence identity, at least 90% sequence identity at least 91% sequence identity, at least 92% sequence identity, at least 93% sequence identity, atleast 94% sequence identity, at least 95% sequence identity, at least 96% sequence identity, at least 97% sequence identity, at least 98% sequence identity, at least 99% sequence identity or 100% sequence identity to the amino acid sequence of SEQ ID NO:35 or a fragment thereof that supports adhesion of PSCs to a substrate.

[0149] In some embodiments, the laminin moiety comprises a laminin beta 2 (β2 or LAMB2) polypeptide or fragment thereof. The full-length amino acid sequence of a representative human laminin beta 2 chain is set forth below, with the signal sequence underlined. MELTSRERGRGQPLPWELRLGLLLSVLAATLAQAPAPDVPGCSRGSCYPATGDLLVGRADRLTASSTCGL NGPQPYCIVSHLQDEKKCFLCDSRRPFSARDNPHSHRIQNVVTSFAPQRRAAWWQSENGIPAVTIQLDLE AEFHFTHLIMTFKTFRPAAMLVERSADFGRTWHVYRYFSYDCGADFPGVPLAPPRHWDDVVCESRYSEIE PSTEGEVIYRVLDPAIPIPDPYSSRIQNLLKITNLRVNLTRLHTLGDNLLDPRREIREKYYYALYELVVR GNCFCYGHASECAPAPGAPAHAEGMVHGACICKHNTRGLNCEQCQDFYRDLPWRPAEDGHSHACRKCECH GHTHSCHFDMAVYLASGNVSGGVCDGCQHNTAGRHCELCRPFFYRDPTKDLRDPAVCRSCDCDPMGSQDG GRCDSHDDPALGLVSGQCRCKEHVVGTRCQQCRDGFFGLSISDRLGCRRCQCNARGTVPGSTPCDPNSGS CYCKRLVTGRGCDRCLPGHWGLSHDLLGCRPCDCDVGGALDPQCDEGTGQCHCRQHMVGRRCEQVQPGYF RPFLDHLIWEAEDTRGQVLDVVERLVTPGETPSWTGSGFVRLQEGQTLEFLVASVPKAMDYDLLLRLEPQ VPEQWAELELIVQRPGPVPAHSLCGHLVPKDDRIQGTLQPHARYLIFPNPVCLEPGISYKLHLKLVRTGG SAQPETPYSGPGLLIDSLVLLPRVLVLEMFSGGDAAALERQATFERYQCHEEGLVPSKTSPSEACAPLLI SLSTLIYNGALPCQCNPQGSLSSECNPHGGQCLCKPGVVGRRCDLCAPGYYGFGPTGCQACQCSHEGALS SLCEKTSGQCLCRTGAFGLRCDRCQRGQWGFPSCRPCVCNGHADECNTHTGACLGCRDHTGGEHCERCIA GFHGDPRLPYGGQCRPCPCPEGPGSQRHFATSCHQDEYSQQIVCHCRAGYTGLRCEACAPGHFGDPSRPG GRCQLCECSGNIDPMDPDACDPHTGQCLRCLHHTEGPHCAHCKPGFHGQAARQSCHRCTCNLLGTNPQQC PSPDQCHCDPSSGQCPCLPNVQGPSCDRCAPNFWNLTSGHGCQPCACHPSRARGPTCNEFTGQCHCRAGF GGRTCSECQELHWGDPGLQCHACDCDSRGIDTPQCHRFTGHCSCRPGVSGVRCDQCARGFSGIFPACHPC HACFGDWDRVVQDLAARTQRLEQRAQELQQTGVLGAFESSFWHMQEKLGIVQGIVGARNTSAASTAQLVE ATEELRREIGEATEHLTQLEADLTDVQDENFNANHALSGLERDRLALNLTLRQLDQHLDLLKHSNFLGAY DSIRHAHSQSAEAERRANTSALAVPSPVSNSASARHRTEALMDAQKEDFNSKHMANQRALGKLSAHTHTL SLTDINELVCGAPGDAPCATSPCGGAGCRDEDGQPRCGGLSCNGAAATADLALGRARHTQAELQRALAEG GSILSRVAETRRQASEAQQRAQAALDKANASRGQVEQANQELQELIQSVKDFLNQEGADPDSIEMVATRV LELSIPASAEQIQHLAGAIAERVRSLADVDAILARTVGDVRRAEQLLQDARRARSWAEDEKQKAETVQAA LEEAQRAQGIAQGAIRGAVADTRDTEQTLYQVQERMAGAERALSSAGERARQLDALLEALKLKRAGNSLA ASTAEETAGSAQGRAQEAEQLLRGPLGDQYQTVKALAERKAQGVLAAQARAEQLRDEARDLLQAAQDKLQ RLQELEGTYEENERALESKAAQLDGLEARMRSVLQAINLQVQIYNTCQ (SEQ ID NO:19)

[0150] In some embodiments, the laminin moiety comprises an amino acid sequence having at least 76% sequence identity to the mature human laminin beta 2 polypeptide chain or fragment thereof. The mature amino acid sequence of the human laminin beta 2 chain represented by SEQ ID NO:19 is set forth below. QAPAPDVPGCSRGSCYPATGDLLVGRADRLTASSTCGLNGPQPYCIVSHLQDEKKCFLCDSRRPFSARDN PHSHRIQNVVTSFAPQRRAAWWQSENGIPAVTIQLDLEAEFHFTHLIMTFKTFRPAAMLVERSADFGRTW HVYRYFSYDCGADFPGVPLAPPRHWDDVVCESRYSEIEPSTEGEVIYRVLDPAIPIPDPYSSRIQNLLKI TNLRVNLTRLHTLGDNLLDPRREIREKYYYALYELVVRGNCFCYGHASECAPAPGAPAHAEGMVHGACIC KHNTRGLNCEQCQDFYRDLPWRPAEDGHSHACRKCECHGHTHSCHFDMAVYLASGNVSGGVCDGCQHNTA GRHCELCRPFFYRDPTKDLRDPAVCRSCDCDPMGSQDGGRCDSHDDPALGLVSGQCRCKEHVVGTRCQQC RDGFFGLSISDRLGCRRCQCNARGTVPGSTPCDPNSGSCYCKRLVTGRGCDRCLPGHWGLSHDLLGCRPC DCDVGGALDPQCDEGTGQCHCRQHMVGRRCEQVQPGYFRPFLDHLIWEAEDTRGQVLDVVERLVTPGETP SWTGSGFVRLQEGQTLEFLVASVPKAMDYDLLLRLEPQVPEQWAELELIVQRPGPVPAHSLCGHLVPKDD RIQGTLQPHARYLIFPNPVCLEPGISYKLHLKLVRTGGSAQPETPYSGPGLLIDSLVLLPRVLVLEMFSG GDAAALERQATFERYQCHEEGLVPSKTSPSEACAPLLISLSTLIYNGALPCQCNPQGSLSSECNPHGGQC LCKPGVVGRRCDLCAPGYYGFGPTGCQACQCSHEGALSSLCEKTSGQCLCRTGAFGLRCDRCQRGQWGFP SCRPCVCNGHADECNTHTGACLGCRDHTGGEHCERCIAGFHGDPRLPYGGQCRPCPCPEGPGSQRHFATSCHQDEYSQQIVCHCRAGYTGLRCEACAPGHFGDPSRPGGRCQLCECSGNIDPMDPDACDPHTGQCLRCLH HTEGPHCAHCKPGFHGQAARQSCHRCTCNLLGTNPQQCPSPDQCHCDPSSGQCPCLPNVQGPSCDRCAPN FWNLTSGHGCQPCACHPSRARGPTCNEFTGQCHCRAGFGGRTCSECQELHWGDPGLQCHACDCDSRGIDT PQCHRFTGHCSCRPGVSGVRCDQCARGFSGIFPACHPCHACFGDWDRVVQDLAARTQRLEQRAQELQQTG VLGAFESSFWHMQEKLGIVQGIVGARNTSAASTAQLVEATEELRREIGEATEHLTQLEADLTDVQDENFN ANHALSGLERDRLALNLTLRQLDQHLDLLKHSNFLGAYDSIRHAHSQSAEAERRANTSALAVPSPVSNSA SARHRTEALMDAQKEDFNSKHMANQRALGKLSAHTHTLSLTDINELVCGAPGDAPCATSPCGGAGCRDED GQPRCGGLSCNGAAATADLALGRARHTQAELQRALAEGGSILSRVAETRRQASEAQQRAQAALDKANASR GQVEQANQELQELIQSVKDFLNQEGADPDSIEMVATRVLELSIPASAEQIQHLAGAIAERVRSLADVDAI LARTVGDVRRAEQLLQDARRARSWAEDEKQKAETVQAALEEAQRAQGIAQGAIRGAVADTRDTEQTLYQV QERMAGAERALSSAGERARQLDALLEALKLKRAGNSLAASTAEETAGSAQGRAQEAEQLLRGPLGDQYQT VKALAERKAQGVLAAQARAEQLRDEARDLLQAAQDKLQRLQELEGTYEENERALESKAAQLDGLEARMRS VLQAINLQVQIYNTCQ (SEQ ID NO:36)

[0151] In some embodiments, the laminin moiety comprises an amino acid sequence having at least 76% sequence identity, at least 77% sequence identity, at least 78% sequence identity, at least 79% sequence identity, at least 80% sequence identity, at least 81% sequence identity, at least 82% sequence identity, at least 83% sequence identity, at least 84% sequence identity, at least 85% sequence identity, at least 86% sequence identity, at least 87% sequence identity, at least 88% sequence identity, at least 89% sequence identity, at least 90% sequence identity at least 91% sequence identity, at least 92% sequence identity, at least 93% sequence identity, at least 94% sequence identity, at least 95% sequence identity, at least 96% sequence identity, at least 97% sequence identity, at least 98% sequence identity, at least 99% sequence identity or 100% sequence identity to the amino acid sequence of SEQ ID NO:36 or a fragment thereof that supports adhesion of PSCs to a substrate.

[0152] In some embodiments, the laminin moiety is a murine laminin beta 2 chain. The full- length amino acid sequence of a representative murine laminin beta 2 chain is set forth below, with the signal sequence underlined. MEWASGEPGR GRQGQPLPWE LRLGLLLSVL AATLAQAPSL DVPGCSRGSC YPATGDLLVG RADRLTASST CGLHSPQPYC IVSHLQDEKK CFLCDSRRPF SARDNPNSHR IQNVVTSFAP QRRTAWWQSE NGVPMVTIQL DLEAEFHFTH LIMTFKTFRP AAMLVERSAD FGRTWHVYRY FSYDCGADFP GIPLAPPRRW DDVVCESRYS EIEPSTEGEV IYRVLDPAIP IPDPYSSRIQ NLLKITNLRV NLTRLHTLGD NLLDPRREIR EKYYYALYEL VIRGNCFCYG HASQCAPAPG APAHAEGMVH GACICKHNTR GLNCEQCQDF YQDLPWHPAE DGHTHACRKC ECNGHTHSCH NVSGGVCDGC QHNTAGRHCE FCRPFFYRDP TKDMRDPAVC RPCDCDPMGS QDGGRCDSHD DPVLGLVSGQ CRCKEHVVGT RCQQCRDGFF GLSASDPRGC QRCQCNSRGT VPGSSPCDSS SGTCFCKRLV TGHGCDRCLP GHWGLSHDLL GCRPCDCDVG GALDPQCDEA TGQCRCRQHM IGRRCEQVQP GYFRPFLDHL TWEAEAAQGQ GLEVVERLVT NRETPSWTGP GFVRLREGQE VEFLVTSLPR AMDYDLLLRW EPQVPEQWAE LELMVQRPGP VSAHSPCGHV LPKDDRIQGM LHPNTRFLVF PRPVCLEPGI SYKLKLKLIG TGGRAQPETS YSGLLIDSLV LQPHVLVLEM FSGGDAAALE RRTTFERYRC HEEGLMPSKA PLSETCAPLL ISVSALIYNG ALPCQCDPQG SLSSECSPHG GQCRCKPGVV GRRCDVCATG YYGFGPAGCQ ACQCSPDGAL SALCEGTSGQ CPCRPGAFGL RCDHCQRGQW GFPNCRPCVC NGRADECDTH TGACLGCRDY TGGEHCERCI AGFHGDPRLP YGGQCRPCPC PEGPGSQRHF ATSCHRDGYS QQIVCQCREG YTGLRCEACA PGHFGDPSKP GGRCQLCECS GNIDPMDPDA CDPHTGQCLR CLHNTEGPHC GYCKPGFHGQ AARQSCHRCT CNLLGTDPRR CPSTDLCHCD PSTGQCPCLP HVQGLNCDHC APNFWNFTSG RGCQPCACHP SRARGPTCNE FTGQCHCHAG FGGRTCSECQ ELYWGDPGLQ CRACDCDPRG IDKPQCHRST GHCSCRPGVS GVRCDQCARG FSGVFPACHP CHACFGDWDR VVQDLAARTR RLEQWAQELQ QTGVLGAFES SFLNMQGKLG MVQAIMSARN ASAASTAKLV EATEGLRHEI GKTTERLTQL EAELTAVQDE NFNANHALSG LERDGLALNL TLRQLDQHLE ILKHSNFLGAYDSIRHAHSQ STEAERRANA STFAVPSPVS NSADTRRRTE VLMGAQKENF NRQHLANQQA LGRLSAHAHT LSLTGINELV CGAPGDAPCA TSPCGGAGCR DEDGQPRCGG LGCSGAAATA DLALGRARHT QAELQRALVE GGGILSRVSE TRRQAEEAQQ RAQAALDKAN ASRGQVEQAN QELRELIQNV KDFLSQEGAD PDSIEMVATR VLDISIPASP EQIQRLASEI AERVRSLADV DTILAHTMGD VRRAEQLLQD AHRARSRAEG ERQKAETVQA ALEEAQRAQG AAQGAIWGAV VDTQNTEQTL QRVQERMAGA EKSLNSAGER ARQLDALLEA LKLKRAGNSL AASTAEETAG SAQSRAREAE KQLREQVGDQ YQTVRALAER KAEGVLAAQA RAEQLRDEAR DLLQAAQDKL QRLQELEGTY EENERALEGK AAQLDGLEAR MRSVLQAINL QVQIYNTCQ (SEQ ID NO:20)

[0153] In some embodiments, the laminin moiety comprises an amino acid sequence having at least 76% sequence identity to the mature murine laminin beta 2 polypeptide chain or fragment thereof. The mature amino acid sequence of the murine laminin beta 2 chain represented by SEQ ID NO:20 is set forth below. QAPSL DVPGCSRGSC YPATGDLLVG RADRLTASST CGLHSPQPYC IVSHLQDEKK CFLCDSRRPF SARDNPNSHR IQNVVTSFAP QRRTAWWQSE NGVPMVTIQL DLEAEFHFTH LIMTFKTFRP AAMLVERSAD FGRTWHVYRY FSYDCGADFP GIPLAPPRRW DDVVCESRYS EIEPSTEGEV IYRVLDPAIP IPDPYSSRIQ NLLKITNLRV NLTRLHTLGD NLLDPRREIR EKYYYALYEL VIRGNCFCYG HASQCAPAPG APAHAEGMVH GACICKHNTR GLNCEQCQDF YQDLPWHPAE DGHTHACRKC ECNGHTHSCH NVSGGVCDGC QHNTAGRHCE FCRPFFYRDP TKDMRDPAVC RPCDCDPMGS QDGGRCDSHD DPVLGLVSGQ CRCKEHVVGT RCQQCRDGFF GLSASDPRGC QRCQCNSRGT VPGSSPCDSS SGTCFCKRLV TGHGCDRCLP GHWGLSHDLL GCRPCDCDVG GALDPQCDEA TGQCRCRQHM IGRRCEQVQP GYFRPFLDHL TWEAEAAQGQ GLEVVERLVT NRETPSWTGP GFVRLREGQE VEFLVTSLPR AMDYDLLLRW EPQVPEQWAE LELMVQRPGP VSAHSPCGHV LPKDDRIQGM LHPNTRFLVF PRPVCLEPGI SYKLKLKLIG TGGRAQPETS YSGLLIDSLV LQPHVLVLEM FSGGDAAALE RRTTFERYRC HEEGLMPSKA PLSETCAPLL ISVSALIYNG ALPCQCDPQG SLSSECSPHG GQCRCKPGVV GRRCDVCATG YYGFGPAGCQ ACQCSPDGAL SALCEGTSGQ CPCRPGAFGL RCDHCQRGQW GFPNCRPCVC NGRADECDTH TGACLGCRDY TGGEHCERCI AGFHGDPRLP YGGQCRPCPC PEGPGSQRHF ATSCHRDGYS QQIVCQCREG YTGLRCEACA PGHFGDPSKP GGRCQLCECS GNIDPMDPDA CDPHTGQCLR CLHNTEGPHC GYCKPGFHGQ AARQSCHRCT CNLLGTDPRR CPSTDLCHCD PSTGQCPCLP HVQGLNCDHC APNFWNFTSG RGCQPCACHP SRARGPTCNE FTGQCHCHAG FGGRTCSECQ ELYWGDPGLQ CRACDCDPRG IDKPQCHRST GHCSCRPGVS GVRCDQCARG FSGVFPACHP CHACFGDWDR VVQDLAARTR RLEQWAQELQ QTGVLGAFES SFLNMQGKLG MVQAIMSARN ASAASTAKLV EATEGLRHEI GKTTERLTQL EAELTAVQDE NFNANHALSG LERDGLALNL TLRQLDQHLE ILKHSNFLGA YDSIRHAHSQ STEAERRANA STFAVPSPVS NSADTRRRTE VLMGAQKENF NRQHLANQQA LGRLSAHAHT LSLTGINELV CGAPGDAPCA TSPCGGAGCR DEDGQPRCGG LGCSGAAATA DLALGRARHT QAELQRALVE GGGILSRVSE TRRQAEEAQQ RAQAALDKAN ASRGQVEQAN QELRELIQNV KDFLSQEGAD PDSIEMVATR VLDISIPASP EQIQRLASEI AERVRSLADV DTILAHTMGD VRRAEQLLQD AHRARSRAEG ERQKAETVQA ALEEAQRAQG AAQGAIWGAV VDTQNTEQTL QRVQERMAGA EKSLNSAGER ARQLDALLEA LKLKRAGNSL AASTAEETAG SAQSRAREAE KQLREQVGDQ YQTVRALAER KAEGVLAAQA RAEQLRDEAR DLLQAAQDKL QRLQELEGTY EENERALEGK AAQLDGLEAR MRSVLQAINL QVQIYNTCQ (SEQ ID NO:37)

[0154] In some embodiments, the laminin moiety comprises an amino acid sequence having at least 76% sequence identity, at least 77% sequence identity, at least 78% sequence identity, at least 79% sequence identity, at least 80% sequence identity, at least 81% sequence identity, at least 82% sequence identity, at least 83% sequence identity, at least 84% sequence identity, at least 85% sequence identity, at least 86% sequence identity, at least 87% sequence identity, at least 88% sequence identity, at least 89% sequence identity, at least 90% sequence identity at least 91% sequence identity, at least 92% sequence identity, at least 93% sequence identity, at least 94% sequence identity, at least 95% sequence identity, at least 96% sequence identity, atleast 97% sequence identity, at least 98% sequence identity, at least 99% sequence identity or 100% sequence identity to the amino acid sequence of SEQ ID NO:37 or a fragment thereof that supports adhesion of PSCs to a substrate.

[0155] In some embodiments, the laminin moiety comprises a laminin gamma 1 (γ1 or LAMC1) polypeptide or fragment thereof. The full-length amino acid sequence of a representative human laminin gamma 1 chain is set forth below, with the signal sequence underlined. MRGSHRAAPALRPRGRLWPVLAVLAAAAAAGCAQAAMDECTDEGGRPQRCMPEFVNAAFNVTVVATNTCG TPPEEYCVQTGVTGVTKSCHLCDAGQPHLQHGAAFLTDYNNQADTTWWQSQTMLAGVQYPSSINLTLHLG KAFDITYVRLKFHTSRPESFAIYKRTREDGPWIPYQYYSGSCENTYSKANRGFIRTGGDEQQALCTDEFS DISPLTGGNVAFSTLEGRPSAYNFDNSPVLQEWVTATDIRVTLNRLNTFGDEVFNDPKVLKSYYYAISDF AVGGRCKCNGHASECMKNEFDKLVCNCKHNTYGVDCEKCLPFFNDRPWRRATAESASECLPCDCNGRSQE CYFDPELYRSTGHGGHCTNCQDNTDGAHCERCRENFFRLGNNEACSSCHCSPVGSLSTQCDSYGRCSCKP GVMGDKCDRCQPGFHSLTEAGCRPCSCDPSGSIDECNIETGRCVCKDNVEGFNCERCKPGFFNLESSNPR GCTPCFCFGHSSVCTNAVGYSVYSISSTFQIDEDGWRAEQRDGSEASLEWSSERQDIAVISDSYFPRYFI APAKFLGKQVLSYGQNLSFSFRVDRRDTRLSAEDLVLEGAGLRVSVPLIAQGNSYPSETTVKYVFRLHEA TDYPWRPALTPFEFQKLLNNLTSIKIRGTYSERSAGYLDDVTLASARPGPGVPATWVESCTCPVGYGGQF CEMCLSGYRRETPNLGPYSPCVLCACNGHSETCDPETGVCNCRDNTAGPHCEKCSDGYYGDSTAGTSSDC QPCPCPGGSSCAVVPKTKEVVCTNCPTGTTGKRCELCDDGYFGDPLGRNGPVRLCRLCQCSDNIDPNAVG NCNRLTGECLKCIYNTAGFYCDRCKDGFFGNPLAPNPADKCKACNCNLYGTMKQQSSCNPVTGQCECLPH VTGQDCGACDPGFYNLQSGQGCERCDCHALGSTNGQCDIRTGQCECQPGITGQHCERCEVNHFGFGPEGC KPCDCHPEGSLSLQCKDDGRCECREGFVGNRCDQCEENYFYNRSWPGCQECPACYRLVKDKVADHRVKLQ ELESLIANLGTGDEMVTDQAFEDRLKEAEREVMDLLREAQDVKDVDQNLMDRLQRVNNTLSSQISRLQNI RNTIEETGNLAEQARAHVENTERLIEIASRELEKAKVAAANVSVTQPESTGDPNNMTLLAEEARKLAERH KQEADDIVRVAKTANDTSTEAYNLLLRTLAGENQTAFEIEELNRKYEQAKNISQDLEKQAARVHEEAKRA GDKAVEIYASVAQLSPLDSETLENEANNIKMEAENLEQLIDQKLKDYEDLREDMRGKELEVKNLLEKGKT EQQTADQLLARADAAKALAEEAAKKGRDTLQEANDILNNLKDFDRRVNDNKTAAEEALRKIPAINQTITE ANEKTREAQQALGSAAADATEAKNKAHEAERIASAVQKNATSTKAEAERTFAEVTDLDNEVNNMLKQLQE AEKELKRKQDDADQDMMMAGMASQAAQEAEINARKAKNSVTSLLSIINDLLEQLGQLDTVDLNKLNEIEG TLNKAKDEMKVSDLDRKVSDLENEAKKQEAAIMDYNRDIEEIMKDIRNLEDIRKTLPSGCFNTPSIEKP (SEQ ID NO:25)

[0156] In some embodiments, the laminin moiety comprises an amino acid sequence having at least 76% sequence identity to the mature human laminin gamma 1 polypeptide chain or fragment thereof. The mature amino acid sequence of the human laminin gamma 1 chain represented by SEQ ID NO:25 is set forth below. QAAMDECTDEGGRPQRCMPEFVNAAFNVTVVATNTCGTPPEEYCVQTGVTGVTKSCHLCDAGQPHLQHGA AFLTDYNNQADTTWWQSQTMLAGVQYPSSINLTLHLGKAFDITYVRLKFHTSRPESFAIYKRTREDGPWI PYQYYSGSCENTYSKANRGFIRTGGDEQQALCTDEFSDISPLTGGNVAFSTLEGRPSAYNFDNSPVLQEW VTATDIRVTLNRLNTFGDEVFNDPKVLKSYYYAISDFAVGGRCKCNGHASECMKNEFDKLVCNCKHNTYG VDCEKCLPFFNDRPWRRATAESASECLPCDCNGRSQECYFDPELYRSTGHGGHCTNCQDNTDGAHCERCR ENFFRLGNNEACSSCHCSPVGSLSTQCDSYGRCSCKPGVMGDKCDRCQPGFHSLTEAGCRPCSCDPSGSI DECNIETGRCVCKDNVEGFNCERCKPGFFNLESSNPRGCTPCFCFGHSSVCTNAVGYSVYSISSTFQIDE DGWRAEQRDGSEASLEWSSERQDIAVISDSYFPRYFIAPAKFLGKQVLSYGQNLSFSFRVDRRDTRLSAE DLVLEGAGLRVSVPLIAQGNSYPSETTVKYVFRLHEATDYPWRPALTPFEFQKLLNNLTSIKIRGTYSER SAGYLDDVTLASARPGPGVPATWVESCTCPVGYGGQFCEMCLSGYRRETPNLGPYSPCVLCACNGHSETC DPETGVCNCRDNTAGPHCEKCSDGYYGDSTAGTSSDCQPCPCPGGSSCAVVPKTKEVVCTNCPTGTTGKR CELCDDGYFGDPLGRNGPVRLCRLCQCSDNIDPNAVGNCNRLTGECLKCIYNTAGFYCDRCKDGFFGNPL APNPADKCKACNCNLYGTMKQQSSCNPVTGQCECLPHVTGQDCGACDPGFYNLQSGQGCERCDCHALGST NGQCDIRTGQCECQPGITGQHCERCEVNHFGFGPEGCKPCDCHPEGSLSLQCKDDGRCECREGFVGNRCD QCEENYFYNRSWPGCQECPACYRLVKDKVADHRVKLQELESLIANLGTGDEMVTDQAFEDRLKEAEREVMDLLREAQDVKDVDQNLMDRLQRVNNTLSSQISRLQNIRNTIEETGNLAEQARAHVENTERLIEIASRELE KAKVAAANVSVTQPESTGDPNNMTLLAEEARKLAERHKQEADDIVRVAKTANDTSTEAYNLLLRTLAGEN QTAFEIEELNRKYEQAKNISQDLEKQAARVHEEAKRAGDKAVEIYASVAQLSPLDSETLENEANNIKMEA ENLEQLIDQKLKDYEDLREDMRGKELEVKNLLEKGKTEQQTADQLLARADAAKALAEEAAKKGRDTLQEA NDILNNLKDFDRRVNDNKTAAEEALRKIPAINQTITEANEKTREAQQALGSAAADATEAKNKAHEAERIA SAVQKNATSTKAEAERTFAEVTDLDNEVNNMLKQLQEAEKELKRKQDDADQDMMMAGMASQAAQEAEINA RKAKNSVTSLLSIINDLLEQLGQLDTVDLNKLNEIEGTLNKAKDEMKVSDLDRKVSDLENEAKKQEAAIM DYNRDIEEIMKDIRNLEDIRKTLPSGCFNTPSIEKP (SEQ ID NO:38)

[0157] In some embodiments, the laminin moiety comprises an amino acid sequence having at least 76% sequence identity, at least 77% sequence identity, at least 78% sequence identity, at least 79% sequence identity, at least 80% sequence identity, at least 81% sequence identity, at least 82% sequence identity, at least 83% sequence identity, at least 84% sequence identity, at least 85% sequence identity, at least 86% sequence identity, at least 87% sequence identity, at least 88% sequence identity, at least 89% sequence identity, at least 90% sequence identity at least 91% sequence identity, at least 92% sequence identity, at least 93% sequence identity, at least 94% sequence identity, at least 95% sequence identity, at least 96% sequence identity, at least 97% sequence identity, at least 98% sequence identity, at least 99% sequence identity or 100% sequence identity to the amino acid sequence of SEQ ID NO:38 or a fragment thereof that supports adhesion of PSCs to a substrate.

[0158] In some embodiments, the laminin moiety is a murine laminin gamma 1 chain. The full- length amino acid sequence of a representative murine gamma 1 chain is set forth below, with the signal sequence underlined. MTGGGRAALA LQPRGRLWPL LAVLAAVAGC VRAAMDECAD EGGRPQRCMP EFVNAAFNVT VVATNTCGTP PEEYCVQTGV TGVTKSCHLC DAGQQHLQHG AAFLTDYNNQ ADTTWWQSQT MLAGVQYPNS INLTLHLGKA FDITYVRLKF HTSRPESFAI YKRTREDGPW IPYQYYSGSC ENTYSKANRG FIRTGGDEQQ ALCTDEFSDI SPLTGGNVAF STLEGRPSAY NFDNSPVLQE WVTATDIRVT LNRLNTFGDE VFNDPKVLKS YYYAISDFAV GGRCKCNGHA SECVKNEFDK LMCNCKHNTY GVDCEKCLPF FNDRPWRRAT AESASECLPC DCNGRSQECY FDPELYRSTG HGGHCTNCRD NTDGAKCERC RENFFRLGNT EACSPCHCSP VGSLSTQCDS YGRCSCKPGV MGDKCDRCQP GFHSLTEAGC RPCSCDPSGS TDECNVETGR CVCKDNVEGF NCERCKPGFF NLESSNPKGC TPCFCFGHSS VCTNAVGYSV YDISSTFQID EDGWRVEQRD GSEASLEWSS DRQDIAVISD SYFPRYFIAP VKFLGNQVLS YGQNLSFSFR VDRRDTRLSA EDLVLEGAGL RVSVPLIAQG NSYPSETTVK YIFRLHEATD YPWRPALSPF EFQKLLNNLT SIKIRGTYSE RSAGYLDDVT LQSARPGPGV PATWVESCTC PVGYGGQFCE TCLPGYRRET PSLGPYSPCV LCTCNGHSET CDPETGVCDC RDNTAGPHCE KCSDGYYGDS TLGTSSDCQP CPCPGGSSCA IVPKTKEVVC THCPTGTAGK RCELCDDGYF GDPLGSNGPV RLCRPCQCND NIDPNAVGNC NRLTGECLKC IYNTAGFYCD RCKEGFFGNP LAPNPADKCK ACACNPYGTV QQQSSCNPVT GQCQCLPHVS GRDCGTCDPG YYNLQSGQGC ERCDCHALGS TNGQCDIRTG QCECQPGITG QHCERCETNH FGFGPEGCKP CDCHHEGSLS LQCKEDGRCE CREGFVGNRC DQCEENYFYN RSWPGCQECP ACYRLVKDKV AEHRVKLQEL ESLIANLGTG DDMVTDQAFE DRLKEAEREV TDLLREAQEV KDVDQNLMDR LQRVNSSLHS QISRLQNIRN TIEETGILAE RARSRVESTE QLIEIASREL EKAKMAAANV SITQPESTGE PNNMTLLAEE ARKLAERHKQ EADDIVRVAK TANETSAEAY NLLLRTLAGE NQTALEIEEL NRKYEQAKNI SQDLEKQAAR VHEEAKRAGD KAVEIYASVA QLTPVDSEAL ENEANKIKKE AADLDRLIDQ KLKDYEDLRE DMRGKEHEVK NLLEKGKAEQ QTADQLLARA DAAKALAEEA AKKGRSTLQE ANDILNNLKD FDRRVNDNKT AAEEALRRIP AINRTIAEAN EKTREAQLAL GNAAADATEA KNKAHEAERI ASAVQKNATS TKADAERTFG EVTDLDNEVN GMLRQLEEAE NELKKKQDDA DQDMMMAGMA SQAAQEAELN ARKAKNSVSS LLSQLNNLLD QLGQLDTVDL NKLNEIEGSL NKAKDEMKAS DLDRKVSDLE SEARKQEAAI MDYNRDIAEI IKDIHNLEDI KKTLPTGCFN TPSIEKP (SEQ ID NO:26)

[0159] In some embodiments, the laminin moiety comprises an amino acid sequence having at least 76% sequence identity to the mature murine laminin beta 2 polypeptide or fragment thereof. The mature amino acid sequence of the murine laminin beta 2 polypeptide represented by SEQ ID NO:26 is set forth below: AMDECAD EGGRPQRCMP EFVNAAFNVT VVATNTCGTP PEEYCVQTGV TGVTKSCHLC DAGQQHLQHG AAFLTDYNNQ ADTTWWQSQT MLAGVQYPNS INLTLHLGKA FDITYVRLKF HTSRPESFAI YKRTREDGPW IPYQYYSGSC ENTYSKANRG FIRTGGDEQQ ALCTDEFSDI SPLTGGNVAF STLEGRPSAY NFDNSPVLQE WVTATDIRVT LNRLNTFGDE VFNDPKVLKS YYYAISDFAV GGRCKCNGHA SECVKNEFDK LMCNCKHNTY GVDCEKCLPF FNDRPWRRAT AESASECLPC DCNGRSQECY FDPELYRSTG HGGHCTNCRD NTDGAKCERC RENFFRLGNT EACSPCHCSP VGSLSTQCDS YGRCSCKPGV MGDKCDRCQP GFHSLTEAGC RPCSCDPSGS TDECNVETGR CVCKDNVEGF NCERCKPGFF NLESSNPKGC TPCFCFGHSS VCTNAVGYSV YDISSTFQID EDGWRVEQRD GSEASLEWSS DRQDIAVISD SYFPRYFIAP VKFLGNQVLS YGQNLSFSFR VDRRDTRLSA EDLVLEGAGL RVSVPLIAQG NSYPSETTVK YIFRLHEATD YPWRPALSPF EFQKLLNNLT SIKIRGTYSE RSAGYLDDVT LQSARPGPGV PATWVESCTC PVGYGGQFCE TCLPGYRRET PSLGPYSPCV LCTCNGHSET CDPETGVCDC RDNTAGPHCE KCSDGYYGDS TLGTSSDCQP CPCPGGSSCA IVPKTKEVVC THCPTGTAGK RCELCDDGYF GDPLGSNGPV RLCRPCQCND NIDPNAVGNC NRLTGECLKC IYNTAGFYCD RCKEGFFGNP LAPNPADKCK ACACNPYGTV QQQSSCNPVT GQCQCLPHVS GRDCGTCDPG YYNLQSGQGC ERCDCHALGS TNGQCDIRTG QCECQPGITG QHCERCETNH FGFGPEGCKP CDCHHEGSLS LQCKEDGRCE CREGFVGNRC DQCEENYFYN RSWPGCQECP ACYRLVKDKV AEHRVKLQEL ESLIANLGTG DDMVTDQAFE DRLKEAEREV TDLLREAQEV KDVDQNLMDR LQRVNSSLHS QISRLQNIRN TIEETGILAE RARSRVESTE QLIEIASREL EKAKMAAANV SITQPESTGE PNNMTLLAEE ARKLAERHKQ EADDIVRVAK TANETSAEAY NLLLRTLAGE NQTALEIEEL NRKYEQAKNI SQDLEKQAAR VHEEAKRAGD KAVEIYASVA QLTPVDSEAL ENEANKIKKE AADLDRLIDQ KLKDYEDLRE DMRGKEHEVK NLLEKGKAEQ QTADQLLARA DAAKALAEEA AKKGRSTLQE ANDILNNLKD FDRRVNDNKT AAEEALRRIP AINRTIAEAN EKTREAQLAL GNAAADATEA KNKAHEAERI ASAVQKNATS TKADAERTFG EVTDLDNEVN GMLRQLEEAE NELKKKQDDA DQDMMMAGMA SQAAQEAELN ARKAKNSVSS LLSQLNNLLD QLGQLDTVDL NKLNEIEGSL NKAKDEMKAS DLDRKVSDLE SEARKQEAAI MDYNRDIAEI IKDIHNLEDI KKTLPTGCFN TPSIEKP (SEQ ID NO:39)

[0160] In some embodiments, the laminin moiety comprises an amino acid sequence having at least 76% sequence identity, at least 77% sequence identity, at least 78% sequence identity, at least 79% sequence identity, at least 80% sequence identity, at least 81% sequence identity, at least 82% sequence identity, at least 83% sequence identity, at least 84% sequence identity, at least 85% sequence identity, at least 86% sequence identity, at least 87% sequence identity, at least 88% sequence identity, at least 89% sequence identity, at least 90% sequence identity at least 91% sequence identity, at least 92% sequence identity, at least 93% sequence identity, at least 94% sequence identity, at least 95% sequence identity, at least 96% sequence identity, at least 97% sequence identity, at least 98% sequence identity, at least 99% sequence identity or 100% sequence identity to the amino acid sequence of SEQ ID NO:39 or a fragment thereof that supports adhesion of PSCs to a substrate.

[0161] Proteolytic studies of laminins have identified a protease-resistant core of the laminin αβγ-trimer, called the E8 fragment or E8 domain, which contains the core integrin-binding domain. In some embodiments, the laminin moiety comprises an E8 domain.

[0162] In some embodiments, the laminin moiety comprises an E8 domain of an alpha 5 laminin chain.

[0163] A representative amino acid sequence of the E8 domain of the human alpha 5 laminin chain is set forth below. AAEDAAG QALQQADHTW ATVVRQGLVD RAQQLLANST ALEEAMLQEQ QRLGLVWAAL QGARTQLRDV RAKKDQLEAH IQAAQAMLAM DTDETSKKIA HAKAVAAEAQ DTATRVQSQL QAMQENVERW QGQYEGLRGQ DLGQAVLDAG HSVSTLEKTL PQLLAKLSIL ENRGVHNASL ALSASIGRVR ELIAQARGAA SKVKVPMKFN GRSGVQLRTP RDLADLAAYT ALKFYLQGPE PEPGQGTEDR FVMYMGSRQA TGDYMGVSLR DKKVHWVYQL GEAGPAVLSI DEDIGEQFAA VSLDRTLQFG HMSVTVERQM IQETKGDTVA PGAEGLLNLR PDDFVFYVGG YPSTFTPPPL LRFPGYRGCI EMDTLNEEVV SLYNFERTFQ LDTAVDRPCA RSKSTGDPWL TDGSYLDGTG FARISFDSQI STTKRFEQEL RLVSYSGVLF FLKQQSQFLC LAVQEGSLVL LYDFGAGLKK AVPLQPPPPL TSASKAIQVF LLGGSRKRVL VRVERATVYS VEQDNDLELA DAYYLGGVPP DQLPPSLRRL FPTGGSVRGC VKGIKALGKY VDLKRLNTTG VSAGCTADLL VGRAMTFHGH GFLRLALSNV APLTGNVYSG FGFHSAQDSA LLYYRASPDG LCQVSLQQGR VSLQLLRTEV KTQAGFADGA PHYVAFYSNA TGVWLYVDDQ LQQMKPHRGP PPELQPQPEG PPRLLLGGLP ESGTIYNFSG CISNVFVQRL LGPQRVFDLQ QNLGSVNVST GCAPALQAQT PGLGPRGLQA TARKASRRSR QPA (SEQ ID NO:4)

[0164] In some embodiments, the laminin moiety comprises an amino acid sequence having at least 76% sequence identity, at least 77% sequence identity, at least 78% sequence identity, at least 79% sequence identity, at least 80% sequence identity, at least 81% sequence identity, at least 82% sequence identity, at least 83% sequence identity, at least 84% sequence identity, at least 85% sequence identity, at least 86% sequence identity, at least 87% sequence identity, at least 88% sequence identity, at least 89% sequence identity, at least 90% sequence identity at least 91% sequence identity, at least 92% sequence identity, at least 93% sequence identity, at least 94% sequence identity, at least 95% sequence identity, at least 96% sequence identity, at least 97% sequence identity, at least 98% sequence identity, at least 99% sequence identity or 100% sequence identity to the amino acid sequence of SEQ ID NO:4.

[0165] A representative amino acid sequence of the E8 domain of the X2 variant human alpha 5 laminin chain is set forth below. AAE DAAGQALQQA DHTWATVVRQ GLVDRAQQLL ANSTALEEAM LQEQQRLGLV WAALQGARTQ LRDVRAKKDQ LEAHIQAAQA MLAMDTDETS KKIAHAKAVA AEAQDTATRV QSQLQAMQEN VERWQGQYEG LRGQDLGQAV LDAGHSVSTL EKTLPQLLAK LSILENRGVH NASLALSASI GRVRELIAQA RGAASKVKVP MKFNGRSGVQ LRTPRDLADL AAYTALKFYL QGPEPEPGQG TEDRFVMYMG SRQATGDYMG VSLRDKKVHW VYQLGEAGPA VLSIDEDIGE QFAAVSLDRT LQFGHMSVTV ERQMIQETKG DTVAPGAEGL LNLRPDDFVF YVGGYPSTFT PPPLLRFPGY RGCIEMDTLN EEVVSLYNFE RTFQLDTAVD RPCARSKSTG DPWLTDGSYL DGTGFARISF DSQISTTKRF EQELRLVSYS GVLFFLKQQS QFLCLAVQEG SLVLLYDFGA GLKKAVPLQP PPPLTSASKA IQVFLLGGSR KRVLVRVERA TVYSVEQDND LELADAYYLG GVPPDQLPPS LRRLFPTGGS VRGCVKGIKA LGKYVDLKRL NTTGVSAGCT ADLLVGRAMT FHGHGFLRLA LSNVAPLTGN VYSGFGFHSA QDSALLYYRA SPDGLCQVSL QQGRVSLQLL RTEVKTQAGF ADGAPHYVAF YSNATGVWLY VDDQLQQMKP HRGPPPELQP QPEGPPRLLL GGLPESGTIY NFSGCISNVF VQRLLGPQRV FDLQQNLGSV NVSTGCAPAL QAQTPGLGPR GLQATARKVG TPGASRRSRQ PA (SEQ ID NO:5)

[0166] In some embodiments, the laminin moiety comprises an amino acid sequence having at least 76% sequence identity, at least 77% sequence identity, at least 78% sequence identity, at least 79% sequence identity, at least 80% sequence identity, at least 81% sequence identity, at least 82% sequence identity, at least 83% sequence identity, at least 84% sequence identity, at least 85% sequence identity, at least 86% sequence identity, at least 87% sequence identity, at least 88% sequence identity, at least 89% sequence identity, at least 90% sequence identity at least 91% sequence identity, at least 92% sequence identity, at least 93% sequence identity, at least 94% sequence identity, at least 95% sequence identity, at least 96% sequence identity, at least 97% sequence identity, at least 98% sequence identity, at least 99% sequence identity or 100% sequence identity to the amino acid sequence of SEQ ID NO:5.

[0167] A representative amino acid sequence of the E8 domain of the murine alpha 5 laminin chain is set forth below. AAEDA AGQALRQASR TWEMVVQRGL AAGARQLLAN SSALEETILG HQGRLGLAQG RLQAAGIQLH NVWARKNQLA AQIQEAQAML AMDTSETSEK IAHAKAVAAE ALSTATHVQS QLQGMQKNVE RWQSQLGGLQ GQDLSQVERD ASSSVSTLEK TLPQLLAKLS RLENRGVHNA SLALSANIGR VRKLIAQARS AASKVKVSMK FNGRSGVRLR TPRDLADLAA YTALKFHIQS PVPAPEPGKN TGDHFVLYMG SRQATGDYMG VSLRNQKVHW VYRLGKAGPT TLSIDENIGE QFAAVSIDRT LQFGHMSVTV EKQMVHEIKG DTVAPGSEGL LNLHPDDFVF YVGGYPSNFT PPEPLRFPGY LGCIEMETLN EEVVSLYNFE QTFMLDTAVD KPCARSKATG DPWLTDGSYL DGSGFARISF EKQFSNTKRF DQELRLVSYN GIIFFLKQES QFLCLAVQEG TLVLFYDFGS GLKKADPLQP PQALTAASKA IQVFLLAGNR KRVLVRVERA TVFSVDQDNM LEMADAYYLG GVPPEQLPLS LRQLFPSGGS VRGCIKGIKA LGKYVDLKRL NTTGISFGCT ADLLVGRTMT FHGHGFLPLA LPDVAPITEV VYSGFGFRGT QDNNLLYYRT SPDGPYQVSL REGHVTLRFM NQEVETQRVF ADGAPHYVAF YSNVTGVWLY VDDQLQLVKS HERTTPMLQL QPEEPSRLLL GGLPVSGTFH NFSGCISNVF VQRLRGPQRV FDLHQNMGSV NVSVGCTPAQ LIETSRATAQ KVSRRSRQPS (SEQ ID NO:6)

[0168] In some embodiments, the laminin moiety comprises an amino acid sequence having at least 76% sequence identity, at least 77% sequence identity, at least 78% sequence identity, at least 79% sequence identity, at least 80% sequence identity, at least 81% sequence identity, at least 82% sequence identity, at least 83% sequence identity, at least 84% sequence identity, at least 85% sequence identity, at least 86% sequence identity, at least 87% sequence identity, at least 88% sequence identity, at least 89% sequence identity, at least 90% sequence identity at least 91% sequence identity, at least 92% sequence identity, at least 93% sequence identity, at least 94% sequence identity, at least 95% sequence identity, at least 96% sequence identity, at least 97% sequence identity, at least 98% sequence identity, at least 99% sequence identity or 100% sequence identity to the amino acid sequence of SEQ ID NO:6.

[0169] In some embodiments, the laminin moiety comprises an E8 domain of a beta 1 laminin chain.

[0170] A representative amino acid sequence of the E8 domain of the human beta1 laminin chain is set forth below.LQHSAADIARAEMLLEEAKRASKSATDVKVTADMVKEALEEAEKAQVAAEKAIKQADEDIQGTQNLLTSI ESETAASEETLFNASQRISELERNVEELKRKAAQNSGEAEYIEKVVYTVKQSAEDVKKTLDGELDEKYKK VENLIAKKTEESADARRKAEMLQNEAKTLLAQANSKLQLLKDLERKYEDNQRYLEDKAQELARLEGEVRS LLKDISQKVAVYSTCL (SEQ ID NO:15)

[0171] In some embodiments, the laminin moiety comprises an amino acid sequence having at least 76% sequence identity, at least 77% sequence identity, at least 78% sequence identity, at least 79% sequence identity, at least 80% sequence identity, at least 81% sequence identity, at least 82% sequence identity, at least 83% sequence identity, at least 84% sequence identity, at least 85% sequence identity, at least 86% sequence identity, at least 87% sequence identity, at least 88% sequence identity, at least 89% sequence identity, at least 90% sequence identity at least 91% sequence identity, at least 92% sequence identity, at least 93% sequence identity, at least 94% sequence identity, at least 95% sequence identity, at least 96% sequence identity, at least 97% sequence identity, at least 98% sequence identity, at least 99% sequence identity or 100% sequence identity to the amino acid sequence of SEQ ID NO:15.

[0172] The minimal amino acid sequence of the E8 domain of the human beta 1 laminin chain is YSTCL (SEQ ID NO:17). In some embodiments, the laminin moiety comprises the amino acid sequence of minimal amino acid sequence of the E8 domain of the human beta 1 laminin chain. For example, in some embodiments, the laminin moiety comprises an amino acid sequence having at least 76% sequence identity, at least 77% sequence identity, at least 78% sequence identity, at least 79% sequence identity, at least 80% sequence identity, at least 81% sequence identity, at least 82% sequence identity, at least 83% sequence identity, at least 84% sequence identity, at least 85% sequence identity, at least 86% sequence identity, at least 87% sequence identity, at least 88% sequence identity, at least 89% sequence identity, at least 90% sequence identity at least 91% sequence identity, at least 92% sequence identity, at least 93% sequence identity, at least 94% sequence identity, at least 95% sequence identity, at least 96% sequence identity, at least 97% sequence identity, at least 98% sequence identity, at least 99% sequence identity or 100% sequence identity to a fragment or all of SEQ ID NO:15 and comprises the amino acid sequence of SEQ ID NO:17.

[0173] A representative amino acid sequence of the E8 domain of the murine beta 1 laminin chain is set forth below. LQ QSAADIARAE LLLEEAKRAS KSATDVKVTA DMVKEALEEA EKAQVAAEKA IKQADEDIQG TQNLLTSIES ETAASEETLT NASQRISKLE RNVEELKRKA AQNSGEAEYI EKVVYSVKQN ADDVKKTLDG ELDEKYKKVE SLIAQKTEES ADARRKAELL QNEAKTLLAQ ANSKLQLLED LERKYEDNQK YLEDKAQELV RLEGEVRSLL KDISEKVAVY STCL (SEQ ID NO:16)

[0174] In some embodiments, the laminin moiety comprises an amino acid sequence having at least 76% sequence identity, at least 77% sequence identity, at least 78% sequence identity, at least 79% sequence identity, at least 80% sequence identity, at least 81% sequence identity, at least 82% sequence identity, at least 83% sequence identity, at least 84% sequence identity, at least 85% sequence identity, at least 86% sequence identity, at least 87% sequence identity, atleast 88% sequence identity, at least 89% sequence identity, at least 90% sequence identity at least 91% sequence identity, at least 92% sequence identity, at least 93% sequence identity, at least 94% sequence identity, at least 95% sequence identity, at least 96% sequence identity, at least 97% sequence identity, at least 98% sequence identity, at least 99% sequence identity or 100% sequence identity to the amino acid sequence of SEQ ID NO:16.

[0175] The minimal amino acid sequence of the E8 domain of the human beta 1 laminin chain is YSTCL (SEQ ID NO:17). In some embodiments, the laminin moiety comprises the amino acid sequence of minimal amino acid sequence of the E8 domain of the human beta 1 laminin chain. For example, in some embodiments, the laminin moiety comprises an amino acid sequence having at least 76% sequence identity, at least 77% sequence identity, at least 78% sequence identity, at least 79% sequence identity, at least 80% sequence identity, at least 81% sequence identity, at least 82% sequence identity, at least 83% sequence identity, at least 84% sequence identity, at least 85% sequence identity, at least 86% sequence identity, at least 87% sequence identity, at least 88% sequence identity, at least 89% sequence identity, at least 90% sequence identity at least 91% sequence identity, at least 92% sequence identity, at least 93% sequence identity, at least 94% sequence identity, at least 95% sequence identity, at least 96% sequence identity, at least 97% sequence identity, at least 98% sequence identity, at least 99% sequence identity or 100% sequence identity to a fragment or all of SEQ ID NO:16 and comprises the amino acid sequence of SEQ ID NO:19.

[0176] In some embodiments, the laminin moiety comprises an E8 domain of a beta 2 laminin chain.

[0177] A representative amino acid sequence of the E8 domain of the human beta 2 laminin chain is set forth below. LARTVGDV RRAEQLLQDA RRARSWAEDE KQKAETVQAA LEEAQRAQGI AQGAIRGAVA DTRDTEQTLY QVQERMAGAE RALSSAGERA RQLDALLEAL KLKRAGNSLA ASTAEETAGS AQGRAQEAEQ LLRGPLGDQY QTVKALAERK AQGVLAAQAR AEQLRDEARD LLQAAQDKLQ RLQELEGTYE ENERALESKA AQLDGLEARM RSVLQAINLQ VQIYNTCQ(SEQ ID NO:21)

[0178] In some embodiments, the laminin moiety comprises an amino acid sequence having at least 76% sequence identity, at least 77% sequence identity, at least 78% sequence identity, at least 79% sequence identity, at least 80% sequence identity, at least 81% sequence identity, at least 82% sequence identity, at least 83% sequence identity, at least 84% sequence identity, at least 85% sequence identity, at least 86% sequence identity, at least 87% sequence identity, at least 88% sequence identity, at least 89% sequence identity, at least 90% sequence identity at least 91% sequence identity, at least 92% sequence identity, at least 93% sequence identity, at least 94% sequence identity, at least 95% sequence identity, at least 96% sequence identity, at least 97% sequence identity, at least 98% sequence identity, at least 99% sequence identity or 100% sequence identity to the amino acid sequence of SEQ ID NO:21.

[0179] The minimal amino acid sequence of the E8 domain of the human beta 2 laminin chain is YNTCQ (SEQ ID NO:23). In some embodiments, the laminin moiety comprises the amino acid sequence of minimal amino acid sequence of the E8 domain of the human beta 1 laminin chain. For example, in some embodiments, the laminin moiety comprises an amino acid sequence having at least 76% sequence identity, at least 77% sequence identity, at least 78% sequence identity, at least 79% sequence identity, at least 80% sequence identity, at least 81% sequence identity, at least 82% sequence identity, at least 83% sequence identity, at least 84% sequence identity, at least 85% sequence identity, at least 86% sequence identity, at least 87% sequence identity, at least 88% sequence identity, at least 89% sequence identity, at least 90% sequence identity at least 91% sequence identity, at least 92% sequence identity, at least 93% sequence identity, at least 94% sequence identity, at least 95% sequence identity, at least 96% sequence identity, at least 97% sequence identity, at least 98% sequence identity, at least 99% sequence identity or 100% sequence identity to a fragment or all of SEQ ID NO:21 and comprises the amino acid sequence of SEQ ID NO:23.

[0180] A representative amino acid sequence of the E8 domain of the mouse beta 2 laminin chain is set forth below. LAHTMGD VRRAEQLLQD AHRARSRAEG ERQKAETVQA ALEEAQRAQG AAQGAIWGAV VDTQNTEQTL QRVQERMAGA EKSLNSAGER ARQLDALLEA LKLKRAGNSL AASTAEETAG SAQSRAREAE KQLREQVGDQ YQTVRALAER KAEGVLAAQA RAEQLRDEAR DLLQAAQDKL QRLQELEGTY EENERALEGK AAQLDGLEAR MRSVLQAINL QVQIYNTCQ (SEQ ID NO:22)

[0181] In some embodiments, the laminin moiety comprises an amino acid sequence having at least 76% sequence identity, at least 77% sequence identity, at least 78% sequence identity, at least 79% sequence identity, at least 80% sequence identity, at least 81% sequence identity, at least 82% sequence identity, at least 83% sequence identity, at least 84% sequence identity, at least 85% sequence identity, at least 86% sequence identity, at least 87% sequence identity, at least 88% sequence identity, at least 89% sequence identity, at least 90% sequence identity at least 91% sequence identity, at least 92% sequence identity, at least 93% sequence identity, at least 94% sequence identity, at least 95% sequence identity, at least 96% sequence identity, at least 97% sequence identity, at least 98% sequence identity, at least 99% sequence identity or 100% sequence identity to the amino acid sequence of SEQ ID NO:22.

[0182] The minimal amino acid sequence of the E8 domain of the mouse beta 2 laminin chain is YNTCQ (SEQ ID NO:24). In some embodiments, the laminin moiety comprises the amino acid sequence of minimal amino acid sequence of the E8 domain of the human beta 1 laminin chain. For example, in some embodiments, the laminin moiety comprises an amino acid sequence having at least 76% sequence identity, at least 77% sequence identity, at least 78% sequence identity, at least 79% sequence identity, at least 80% sequence identity, at least 81% sequence identity, at least 82% sequence identity, at least 83% sequence identity, at least 84% sequence identity, at least 85% sequence identity, at least 86% sequence identity, at least 87%sequence identity, at least 88% sequence identity, at least 89% sequence identity, at least 90% sequence identity at least 91% sequence identity, at least 92% sequence identity, at least 93% sequence identity, at least 94% sequence identity, at least 95% sequence identity, at least 96% sequence identity, at least 97% sequence identity, at least 98% sequence identity, at least 99% sequence identity or 100% sequence identity to a fragment or all of SEQ ID NO:22 and comprises the amino acid sequence of SEQ ID NO:24.

[0183] In some embodiments, the laminin moiety comprises an E8 domain of a gamma 1 laminin chain.

[0184] A representative amino acid sequence of the E8 domain of the human gamma 1 laminin chain is set forth below. NDILNNLKDFDRRVNDNKTAAEEALRKIPAINQTITEANEKTREAQQALGSAAADATEAKNKAHEAERIA SAVQKNATSTKAEAERTFAEVTDLDNEVNNMLKQLQEAEKELKRKQDDADQDMMMAGMASQAAQEAEINA RKAKNSVTSLLSIINDLLEQLGQLDTVDLNKLNEIEGTLNKAKDEMKVSDLDRKVSDLENEAKKQEAAIM DYNRDIEEIMKDIRNLEDIRKTLPSGCFNTPSIEKP (SEQ ID NO:27)

[0185] In some embodiments, the laminin moiety comprises an amino acid sequence having at least 76% sequence identity, at least 77% sequence identity, at least 78% sequence identity, at least 79% sequence identity, at least 80% sequence identity, at least 81% sequence identity, at least 82% sequence identity, at least 83% sequence identity, at least 84% sequence identity, at least 85% sequence identity, at least 86% sequence identity, at least 87% sequence identity, at least 88% sequence identity, at least 89% sequence identity, at least 90% sequence identity at least 91% sequence identity, at least 92% sequence identity, at least 93% sequence identity, at least 94% sequence identity, at least 95% sequence identity, at least 96% sequence identity, at least 97% sequence identity, at least 98% sequence identity, at least 99% sequence identity or 100% sequence identity to the amino acid sequence of SEQ ID NO:27.

[0186] The minimal amino acid sequence of the E8 domain of the human gamma 1 laminin chain is PSGCFNTPSIEKP (SEQ ID NO:29). In some embodiments, the laminin moiety comprises the amino acid sequence of minimal amino acid sequence of the E8 domain of the human beta 1 laminin chain. For example, in some embodiments, the laminin moiety comprises an amino acid sequence having at least 76% sequence identity, at least 77% sequence identity, at least 78% sequence identity, at least 79% sequence identity, at least 80% sequence identity, at least 81% sequence identity, at least 82% sequence identity, at least 83% sequence identity, at least 84% sequence identity, at least 85% sequence identity, at least 86% sequence identity, at least 87% sequence identity, at least 88% sequence identity, at least 89% sequence identity, at least 90% sequence identity at least 91% sequence identity, at least 92% sequence identity, at least 93% sequence identity, at least 94% sequence identity, at least 95% sequence identity, at least 96% sequence identity, at least 97% sequence identity, at least 98% sequence identity, at least 99% sequence identity or 100% sequence identity to a fragment or all of SEQ ID NO:27 and comprises the amino acid sequence of SEQ ID NO:29.

[0187] A representative amino acid sequence of the E8 domain of the mouse gamma 1 laminin chain is set forth below. NDILNNLKD FDRRVNDNKT AAEEALRRIP AINRTIAEAN EKTREAQLAL GNAAADATEA KNKAHEAERI ASAVQKNATS TKADAERTFG EVTDLDNEVN GMLRQLEEAE NELKKKQDDA DQDMMMAGMA SQAAQEAELN ARKAKNSVSS LLSQLNNLLD QLGQLDTVDL NKLNEIEGSL NKAKDEMKAS DLDRKVSDLE SEARKQEAAI MDYNRDIAEI IKDIHNLEDI KKTLPTGCFN TPSIEKP (SEQ ID NO:28)

[0188] In some embodiments, the laminin moiety comprises an amino acid sequence having at least 76% sequence identity, at least 77% sequence identity, at least 78% sequence identity, at least 79% sequence identity, at least 80% sequence identity, at least 81% sequence identity, at least 82% sequence identity, at least 83% sequence identity, at least 84% sequence identity, at least 85% sequence identity, at least 86% sequence identity, at least 87% sequence identity, at least 88% sequence identity, at least 89% sequence identity, at least 90% sequence identity at least 91% sequence identity, at least 92% sequence identity, at least 93% sequence identity, at least 94% sequence identity, at least 95% sequence identity, at least 96% sequence identity, at least 97% sequence identity, at least 98% sequence identity, at least 99% sequence identity or 100% sequence identity to the amino acid sequence of SEQ ID NO:28.

[0189] The minimal amino acid sequence of the E8 domain of the mouse gamma 1 laminin chain is PTGCFNTPSIEKP (SEQ ID NO:30). In some embodiments, the laminin moiety comprises the amino acid sequence of minimal amino acid sequence of the E8 domain of the human beta 1 laminin chain. For example, in some embodiments, the laminin moiety comprises an amino acid sequence having at least 76% sequence identity, at least 77% sequence identity, at least 78% sequence identity, at least 79% sequence identity, at least 80% sequence identity, at least 81% sequence identity, at least 82% sequence identity, at least 83% sequence identity, at least 84% sequence identity, at least 85% sequence identity, at least 86% sequence identity, at least 87% sequence identity, at least 88% sequence identity, at least 89% sequence identity, at least 90% sequence identity at least 91% sequence identity, at least 92% sequence identity, at least 93% sequence identity, at least 94% sequence identity, at least 95% sequence identity, at least 96% sequence identity, at least 97% sequence identity, at least 98% sequence identity, at least 99% sequence identity or 100% sequence identity to a fragment or all of SEQ ID NO:28 and comprises the amino acid sequence of SEQ ID NO:30.

[0190] In some embodiments, the laminin moiety comprises an E8 domain of a laminin 521 protein or an E8 domain of a laminin 511 protein. In some embodiments, the E8 domain of the laminin 521 protein comprises an E8 domain of an alpha 5 laminin polypeptide (e.g., having an amino acid sequence of any one of SEQ ID NO:4, SEQ ID NO:5, or SEQ ID NO:6, or an amino acid sequence having at least 77% sequence identity to any one of SEQ ID NOs:4-6), an E8 domain of a beta 2 laminin polypeptide, and an E8 domain of a gamma 1 laminin polypeptide.

[0191] In some embodiments, the E8 domain of the laminin 511 protein comprises an E8 domain of an alpha 5 laminin polypeptide (e.g., having an amino acid sequence of any one of SEQ ID NO:4, SEQ ID NO:5, or SEQ ID NO:6, or an amino acid sequence having at least 77% sequence identity to any one of SEQ ID NOs:4-6), an E8 domain of a beta 1 laminin polypeptide, and an E8 domain of a gamma 1 laminin polypeptide.

[0192] In some embodiments, the E8 domain of the beta 1 laminin polypeptide comprises an amino acid sequence of any one of SEQ ID NOs:15-18 or an amino acid sequence having at least 90% sequence identity to any one of SEQ ID NOs:15-18.

[0193] In some embodiments, the E8 domain of the beta 2 laminin polypeptide comprises an amino acid sequence of any one of SEQ ID NOs:21-24 or an amino acid sequence having at least 90% sequence identity to any one of SEQ ID NOs:19-24.

[0194] In some embodiments, the E8 domain of the gamma 1 laminin polypeptide comprises an amino acid sequence of any one of SEQ ID NOs:27-30 or an amino acid sequence having at least 89% sequence identity to any one of SEQ ID NOs:27-30.

[0195] In some embodiments, the laminin moiety comprises an E8 domain of a laminin 521 protein or an E8 domain of a laminin 511 protein.

[0196] In one embodiment, the E8 domain of a laminin 521 protein comprises peptides or polypeptides having amino acid sequences of (i) SEQ ID NOS:4, 21, and 27; (ii) SEQ ID NOS:5, 21, and 27; (iii) SEQ ID NOS:4, 21, and 29; (iv) SEQ ID NOS:5, 21, and 29; (v) SEQ ID NOS:6, 22, and 28; or (vi) SEQ ID NOS:6, 22, and 30.

[0197] In one embodiment, the E8 domain of a laminin 511 protein comprises peptides or polypeptides having amino acid sequences of (i) SEQ ID NOS:4, 15, and 27; (ii) SEQ ID NOS:4, 15, and 29; (iii) SEQ ID NOS:5, 15, and 27; (iv) SEQ ID NOS:5, 15, and 29; (v) SEQ ID NOS:6, 16, and 28; or (vi) SEQ ID NOS:6, 16, and 30.

[0198] In some embodiments, the laminin moiety is a chimeric fusion protein comprising an E8 domain of a laminin 521 protein (e.g., comprising peptides or polypeptides having amino acid sequences of SEQ ID NOs:4,21, and 27; SEQ ID NOs:4, 21, and 29; SEQ ID NOs:5, 21, and 27; SEQ ID NOs:5, 21, and 29; SEQ ID NOs:6, 22, and 28; or SEQ ID NOs:6, 22, and 30) or an E8 domain of a laminin 511 protein (e.g., comprising peptides or polypeptides having amino acid sequences of SEQ ID NOs:4, 15, and 27; SEQ ID NOs:4, 15, and 29; SEQ ID NOs: 5, 15, and 27; SEQ ID NOs:5, 15, and 29; SEQ ID NOs: 6, 16, and 28; or SEQ ID NOs:6, 16, and 30).

[0199] In some embodiments, the laminin moiety comprises a full-length laminin 521 protein or a full-length laminin 511 protein.

[0200] In one embodiment, the full length laminin 521 protein comprises (i) a laminin alpha 5 polypeptide having an amino acid sequence of SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33,an amino acid sequence having at least 79% sequence identity to SEQ ID NO:1, an amino acid sequence having at least 79% sequence identity to SEQ ID NO:2, or an amino acid sequence having at least 79% sequence identity to SEQ ID NO:3; (ii) a laminin beta 2 polypeptide having an amino acid sequence of SEQ ID NO:36, SEQ ID NO:37, an amino acid sequence having at least 90% sequence identity to SEQ ID NO:19, or an amino acid sequence having at least 90% sequence identity to SEQ ID NO:20; and (iii) a laminin gamma 1 polypeptide having an amino acid sequence of SEQ ID NO:38, an amino acid sequence of SEQ ID NO:39, an amino acid sequence having at least 90% sequence identity to SEQ ID NO:25, or an amino acid sequence having at least 90% sequence identity to SEQ ID NO:26.

[0201] In one embodiment, the full length laminin 511 protein comprises (i) a laminin alpha 5 polypeptide having an amino acid sequence of SEQ ID NO:31, an amino acid sequence SEQ ID NO:32, an amino acid sequence SEQ ID NO:33, an amino acid sequence having at least 79% sequence identity to SEQ ID NO:1, an amino acid sequence having at least 79% sequence identity to SEQ ID NO:2, or an amino acid sequence having at least 79% sequence identity to SEQ ID NO:3; (ii) a laminin beta 2 polypeptide having an amino acid sequence of SEQ ID NO:34, an amino acid sequence SEQ ID NO:35, e an amino acid sequence having at least 90% sequence identity to SEQ ID NO:13, or an amino acid sequence having at least 90% sequence identity to SEQ ID NO:14; and (iii) a laminin gamma 1 polypeptide having an amino acid sequence of SEQ ID NO:38, an amino acid sequence SEQ ID NO:39, an amino acid sequence having at least 90% sequence identity to SEQ ID NO:25, or an amino acid sequence having at least 90% sequence identity to SEQ ID NO:26.

[0202] The laminin-type globular (LG) domains of laminin alpha chains mediate various cellular interactions. For instance, the LG1, LG2, and LG3 tandem of laminin alpha 5 E8 domain has been implicated in integrin and Lu / B-CAM binding. In some embodiments, the laminin moiety comprises a fragment of an E8 domain of an alpha 5 laminin polypeptide. Representative amino acid sequences of human LG1, LG2, and LG3 domains of human laminin alpha 5 E8 domain are set forth below and correspond to SEQ ID NOs: 7, 9, and 11, respectively. PMKFN GRSGVQLRTP RDLADLAAYT ALKFYLQGPE PEPGQGTEDR FVMYMGSRQA TGDYMGVSLR DKKVHWVYQL GEAGPAVLSI DEDIGEQFAA VSLDRTLQFG HMSVTVERQM IQETKGDTVA PGAEGLLNLR PDDFVFYVGG YPSTFTPPPL LRFPGYRGCI EMDTLNEEVV SLYNFERTFQ LDTAVDRPC (SEQ ID NO:7) TDGSYLDGTG FARISFDSQI STTKRFEQEL RLVSYSGVLF FLKQQSQFLC LAVQEGSLVL LYDFGAGLKK AVPLQPPPPL TSASKAIQVF LLGGSRKRVL VRVERATVYS VEQDNDLELA DAYYLGGVPP DQLPPSLRRL FPTGGSVRGC VKGIKALGKY VDLKRLNTTG VSAGC (SEQ ID NO:9) VGRAMTFHGH GFLRLALSNV APLTGNVYSG FGFHSAQDSA LLYYRASPDG LCQVSLQQGR VSLQLLRTEV KTQAGFADGA PHYVAFYSNA TGVWLYVDDQ LQQMKPHRGP PPELQPQPEG PPRLLLGGLP ESGTIYNFSG CISNVFVQRL LGPQRVFDLQ QNLGSVNVST GCA (SEQ ID NO:11)

[0203] Representative amino acid sequences of murine LG1, LG2, and LG3 domains of human laminin alpha 5 E8 domain are set forth below and correspond to SEQ ID NOs: 8, 10, and 12, respectively. M KFNGRSGVRL RTPRDLADLA AYTALKFHIQ SPVPAPEPGK NTGDHFVLYM GSRQATGDYM GVSLRNQKVH WVYRLGKAGP TTLSIDENIG EQFAAVSIDR TLQFGHMSVT VEKQMVHEIK GDTVAPGSEG LLNLHPDDFV FYVGGYPSNF TPPEPLRFPG YLGCIEMETL NEEVVSLYNF EQTFMLDTAV DKPC (SEQ ID NO:8) TDGSY LDGSGFARIS FEKQFSNTKR FDQELRLVSY NGIIFFLKQE SQFLCLAVQE GTLVLFYDFG SGLKKADPLQ PPQALTAASK AIQVFLLAGN RKRVLVRVER ATVFSVDQDN MLEMADAYYL GGVPPEQLPL SLRQLFPSGG SVRGCIKGIK ALGKYVDLKR LNTTGISFGC (SEQ ID NO:10) VGRTMTFHGHGFLPL ALPDVAPITE VVYSGFGFRG TQDNNLLYYR TSPDGPYQVS LREGHVTLRF MNQEVETQRV FADGAPHYVA FYSNVTGVWL YVDDQLQLVK SHERTTPMLQ LQPEEPSRLL LGGLPVSGTF HNFSGCISNV FVQRLRGPQR VFDLHQNMGS VNVSVGC (SEQ ID NO:12)

[0204] In some embodiments, the fragment of the E8 domain of the alpha 5 laminin polypeptide comprises an LG1 fragment. In some embodiments, the LG1 fragment is a human LG1 fragment. In some embodiments, the LG1 fragment comprises an amino acid sequence having at least 82%, at least 87%, at least 90%, or at least 95% sequence identity to the amino acid sequence of SEQ ID NO:7. In some embodiments, the LG1 fragment comprises an amino acid sequence of SEQ ID NO:7.

[0205] In some embodiments, the fragment of the E8 domain of the alpha 5 laminin polypeptide comprises an LG2 fragment. In some embodiments, the LG2 fragment is a human LG2 fragment. In some embodiments, the LG2 fragment comprises an amino acid sequence having at least 85%, at least 90%, or at least 95% sequence identity to the amino acid sequence of SEQ ID NO:9. In some embodiments, the LG2 fragment comprises an amino acid sequence of SEQ ID NO:9.

[0206] In some embodiments, the fragment of the E8 domain of the alpha 5 laminin polypeptide comprises an LG3 fragment. In some embodiments, the LG3 fragment is a human LG3 fragment. In some embodiments, the LG3 fragment comprises an amino acid sequence having at least 73%, at least 80%, at least 85%, at least 90%, or at least 95% sequence identity to the amino acid sequence of SEQ ID NO:11. In some embodiments, the LG3 fragment comprises an amino acid sequence of SEQ ID NO:11.

[0207] In some embodiments, the LG1 fragment is a murine LG1 fragment. In some embodiments, the LG1 fragment comprises an amino acid sequence having at least 82%, at least 87%, at least 90%, or at least 95% sequence identity to the amino acid sequence of SEQ ID NO:8. In some embodiments, the LG1 fragment comprises an amino acid sequence of SEQ ID NO:8.

[0208] In some embodiments, the LG2 fragment is a murine LG2 fragment. In some embodiments, the LG2 fragment comprises an amino acid sequence having at least at least 80%, at least 85%, at least 90%, or at least 95% sequence identity to the amino acid sequence of SEQ ID NO:10. In some embodiments, the LG2 fragment comprises an amino acid sequence of SEQ ID NO:10.

[0209] In some embodiments, the LG3 fragment is a murine LG3 fragment. In some embodiments, the LG3 fragment comprises an amino acid sequence having at least 73%, at least 80%, at least 85%, at least 90%, or at least 95% sequence identity to the amino acid sequence of SEQ ID NO:12. In some embodiments, the LG3 fragment comprises an amino acid sequence of SEQ ID NO:12.

[0210] While in some embodiments the laminin moiety (e.g., full length laminin, laminin fragments such as E8 and others, and chimeras containing laminin sequences) comprises laminin 521 protein and laminin 511 protein, and E8 fragments, isoforms thereof, closely related homologs from one or more species thereof, chimeras, and combinations thereof, one skilled in the art will recognize that other laminins, E8 fragments, homologs and orthologs thereof, and chimeras can be or are useful in the practice of aspects of the disclosure. Thus, in some embodiments, the subject laminin protein is any laminin protein, subunit, chimera, or fragment that enables pluripotent stem cell proliferation while maintaining genetic stability, pluripotency, and selecting against accumulation of BCOR mutations or variant alleles over passages of up to 15, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, or 200 passages. In some embodiments, the subject laminin protein includes any one or more of laminin 111 protein, laminin 121 protein, laminin 211 protein, laminin 221 protein, laminin 323 protein, laminin 332 protein, laminin 411 protein, laminin 421 protein, laminin 523 protein, homologs thereof, and orthologs thereof. In some embodiments, the laminin protein, subunit, fragment, or amino acid sequence is animal, vertebrate, mammalian, murine, primate, or human.

[0211] A laminin moiety can be synthesized or recombinantly produced using methods well known to the skilled person. Laminin moieties are also commercially available, e.g., from BioLamina. In some embodiments, the laminin moiety is one or more of LN521 (BioLamina), MX521 (BioLamina), CT521 (BioLamina), LN111 (BioLamina), LN121 (BioLamina), LN211 (BioLamina), LN221 (BioLamina), LN332 (BioLamina), LN411 (BioLamina), LN421 (BioLamina), LN511 (BioLamina), Biosilk (BioLamina), or Biosilk 521 (BioLamina).

[0212] In one embodiment, the laminin moiety is CT521 (BioLamina).

[0213] In some embodiments, the laminin moiety is coated on the surface of a cell culture container prior to passaging a cell population into the container. In some embodiments, the surface of the cell culture container is coated with a laminin moiety by contacting the surface ofthe cell culture container with the laminin moiety at a concentration of about 0.1 – 10 micrograms, 0.25 – 7.5 micrograms, 0.5 – 5 micrograms, or 1 – 4 micrograms of the laminin moiety per square centimeter of such surface (e.g., about 0.1, 0.25, 0.5, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9., 9.5, or 10 micrograms of the laminin moiety per square centimeter of said substrate). In some embodiments, the laminin moiety is adhered to a substrate at a concentration of 1-150 picomoles (e.g., about 1, 2, 5, 10, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 90, 100, 110, 120, 130, 140, or 150 picomoles) of the laminin moiety per square centimeter of such surface.

[0214] In some embodiments, the laminin moiety is combined with cells during or before passaging into a cell culture container. The cell culture can be coated with a laminin moiety or uncoated with a laminin moiety.

[0215] Suitable cell culture containers that can be coated with a laminin moiety and / or into which a PSC cell culture can be passaged in combination with a laminin moiety, are described in Section 6.4. 6.7. Ancestral Cells

[0216] The genomically stabilized population of pluripotent stem cells (PSCs) of the disclosure is a descendant of an ancestral cell population. The ancestral cell population can be a population of induced pluripotent stem cells, embryonic pluripotent stem cells, adult stem cells, and fetal stem cells. In some embodiments, the ancestral cell population is a human cell population, i.e., a cell population of human origins.

[0217] In some embodiments, the genomically stabilized population of pluripotent stem cells is a population of, or descended from an ancestral cell population comprising, human induced pluripotent stem cells (iPSCs) obtained by reprogramming cells of a hematopoietic origin.

[0218] In some embodiments, the ancestral cell population is an iPSC population generated using a non-integrating vector or episomal vector, e.g., an alphavirus vector, encoding reprogramming factors.

[0219] In some embodiments, the ancestral cell population is an iPSC population generated by reprogramming a hematopoietic cell.

[0220] In some embodiments, the ancestral cell population is an iPSC population generated by reprogramming a hematopoietic cell using any combination of the reprogramming factors, alphavirus vectors, reprogramming methods described in WO / 2022 / 204567, the contents of which are incorporated by reference herein in their entireties.

[0221] In some embodiments, the ancestral cell population comprises or consists of cells a stem cell colony, e.g., an iPSC colony.

[0222] In some embodiments, the ancestral cell population comprises or consists of isogenic cells. 6.8. Assays

[0223] The present disclosure provides methods of testing a PSC population, e.g., to determine whether it is a genomically stabilized population of PSCs, by testing for the prevalence of one or more markers of tumorigenic potential. In some embodiments, the PSC population is a genomically stabilized population of PSCs if the prevalence of one or more markers of tumorigenic potential is below a threshold amount.

[0224] In some embodiments, a sample, e.g., a nucleic acid sample (for example a mRNA sample, a cDNA sample, or a genomic DNA sample), is prepared from a PSC population. The sample can then be subject to PCR amplification. In some embodiments, the PCR amplification process allows for the direct detection of one or more markers of tumorigenic potential. In some embodiments, the PCR amplification process results in a product that can be sequenced to detect the one or more markers of tumorigenic potential.

[0225] In some embodiments, the one or more markers of tumorigenic potential comprise a mutant BCL6 Corepressor (“BCOR”) gene, resulting in one or more mutations relative to the nucleotide sequence of SEQ ID NO:40. In some embodiments, the mutant BCOR gene has a c.572G>A mutation relative to the nucleotide sequence of SEQ ID NO:40 (“BCOR SNP1”) (e.g., resulting in a transcript comprising the nucleotide sequence of SEQ ID NO:41 or SEQ ID NO:43) and / or a c.4819+1G>A mutation relative to the nucleotide sequence of SEQ ID NO:40 (“BCOR SNP2”) (e.g., resulting in a transcript comprising the nucleotide sequence of SEQ ID NO:42 or SEQ ID NO:43).

[0226] In some embodiments, the one or more markers of tumorigenic potential comprise a mutant retinoic acid receptor alpha (“RARA”) gene, resulting in one or more mutations relative to the nucleotide sequence of SEQ ID NO:44. In some embodiments, the mutant RARA gene has a c.352G>T mutation relative to the nucleotide sequence of SEQ ID NO:44 (RARA SNP) (e.g., resulting in a transcript comprising the nucleotide sequence of SEQ ID NO:45).

[0227] In some embodiments, the assays of the disclosure can be used to assess whether a PSC cell population is genomically stabilized. In some embodiments, an assay of the disclosure is performed and the PSC cell population is deemed genomically stabilized if: (i) the prevalence of BCOR SNP1 in the PSC cell population is less than 10%, optionally wherein the cell population is deemed genomically stabilized if the prevalence of BCOR SNP1 in the cell population is less than 5%, less than 1%, less than 0.5%, less than 0.1%, less than 0.05%, less than 0.01%, or if BCOR SNP1 is undetectable in the cell population;(ii) the prevalence of BCOR SNP2 in the PSC cell population is less than 10%, optionally wherein the cell population is deemed genomically stabilized if the prevalence of BCOR SNP2 in the cell population is less than 5%, less than 1%, less than 0.5%, less than 0.1%, less than 0.05%, less than 0.01%, or if BCOR SNP2 is undetectable in the cell population; (iii) the prevalence of RARA SNP in the PSC cell population is less than 10%, optionally wherein the cell population is deemed genomically stabilized if the prevalence of RARA SNP in the cell population is less than 5%, less than 1%, less than 0.5%, less than 0.1%, less than 0.05%, less than 0.01%, or if RARA SNP is undetectable in the cell population; (iv) any combination of two or all three of (i), (ii) and (iii).

[0228] In some embodiments, the PSC cell population is deemed genomically stabilized if the prevalence of at least one, any two of or all three of BCOR SNP1, BCOR SNP2 and RARA SNP is less than 1%.

[0229] In some embodiments, the PSC cell population is deemed genomically stabilized if the prevalence of at least one, any two of or all three of BCOR SNP1, BCOR SNP2 and RARA SNP is less than 0.5%.

[0230] In some embodiments, the PSC cell population is deemed genomically stabilized if the prevalence of at least one, any two of or all three of BCOR SNP1, BCOR SNP2 and RARA SNP is less than 0.1%.

[0231] In some embodiments, the PSC cell population is deemed genomically stabilized if at least one, any two of or all three of BCOR SNP1, BCOR SNP2 and RARA SNP are undetectable in the population.

[0232] The prevalence of one or more markers of tumorigenic potential can be determined by estimating the number (or amount) of each variant allele in a cell population and dividing that number by the total number (or total amount) of all copies of the allele of interest in that cell population.

[0233] In some embodiments, the relative amount of a variant allele in a PSC cell population is determined by using hybridization methods, such as dynamic allele-specific hybridization, oligonucleotide molecular beacon hybridization, sequence-specific oligonucleotide array hybridization, and the like. In some embodiments, the relative amount of a variant allele in a population is determined by using enzyme-based methods, such as restriction fragment length polymorphism quantification, tetra-primer amplification refractory mutation systems PCR (ARMS-PCR), flap endonuclease basic invader or SISAR invader assays, primer extension assays, 5-prime nuclease assays, oligonucleotide ligation assays, and the like. In someembodiments, the relative amount of a variant allele in a population is determined by using quantitative or semi-quantitative PCR-based methods, such as digital PCR (dPCR), differential display PCR, droplet digital PCR (ddPCR), and the like. See, e.g., Vossen and White, Methods Mol Biol.2017;1492:167-177. In some embodiments, the relative amount of a variant allele in a population is determined by using high throughput nucleic acid sequencing (HTS) methods, such as next generation sequencing (NGS), ion torrent, Roche 454 sequencing, Hiseq, Hi5 NGS, targeted NGS, PacBio RS, third generation sequencing, transcriptome sequencing, nanopore sequencing, and the like. See, e.g., Sukhai et al., J Molecular Diagnostics 2019; 21(2):261-273.

[0234] In some embodiments, the relative amount of a variant allele in a PSC cell population is determined by using quantitative PCR methods (e.g., digital droplet PCR or ddPCR) or semi- quantitative PCR-based methods.

[0235] In some embodiments, the relative amount of a variant allele in a PSC cell population is determined by using high throughput nucleic acid sequencing (HTS) methods, for example using a next-generation sequencing (NGS) assay.

[0236] If it is determined that the PSC cell population has a prevalence of one or more markers of tumorigenic potential below a desirable cutoff amount, its cells can be cryopreserved or banked for later use, expanded, or differentiated into cells to formulate into a cell therapy.

[0237] If it is determined that the PSC cell population has a prevalence of one or more markers of tumorigenic potential above a desirable cutoff amount, its cells can be discarded. Alternatively, the cells can be cultured under conditions described herein (e.g., as described in Section 6.3) for generating genomically stabilized cell populations. Optionally, once a PSC cell population is produced in which the prevalence of one or more markers of tumorigenic potential below a desired cutoff amount, its cells can be cryopreserved or banked for later use, maintained or expanded in culture, or differentiated into cells to formulate into a cell therapy. In some embodiments, the PSC cell population in which the prevalence of one or more markers of tumorigenic potential is below a desired cutoff amount is a genomically stabilized cell populations. 6.9. Use of Genomically Stabilized Cell Populations to Produce Cell Therapy

[0238] The genomically stabilized populations of PSCs can advantageously be used to generate and / or maintain differentiated cells with reduced tumorigenic potential and thus useful for cell therapy.

[0239] Accordingly, in some embodiments, a genomically stabilized population of PSCs is differentiated and optionally formulated as a cell therapy.

[0240] In some embodiments, genomically stabilized population of PSCs is differentiated into a cell population comprising or consisting of human immune cells, for example T cells, T cells expressing a chimeric antigen receptor (CAR), suppressive T cells, myeloid cells, dendritic cells, or immunosuppressive macrophages.

[0241] In some embodiments, genomically stabilized population of PSCs is differentiated into a cell population comprising or consisting of cells in the human nervous system, for example dopaminergic neurons, microglial cells, oligodendrocytes, astrocytes, cortical neurons, spinal or oculomotor neurons, enteric neurons, placode-derived cells, Schwann cells, and trigeminal or sensory neurons.

[0242] In some embodiments, genomically stabilized population of PSCs is differentiated into a cell population comprising or consisting of cells in the human cardiovascular system, for example from cardiomyocytes, endothelial cells, or nodal cells.

[0243] In some embodiments, genomically stabilized population of PSCs is differentiated into a cell population comprising or consisting of cells in the human metabolic system, for example hepatocytes, cholangiocytes, or pancreatic beta cells.

[0244] In some embodiments, genomically stabilized population of PSCs is differentiated into a cell population comprising or consisting of cells in the human ocular system, for example retinal pigment epithelial cells, a photoreceptor cone cells, photoreceptor rod cells, bipolar cells, or ganglion cells.

[0245] In some embodiments, the differentiated cells are formulated with a pharmaceutically acceptable carrier or excipient for use in cell therapy. 7. SPECIFIC EMBODIMENTS

[0246] The present disclosure is exemplified by the specific embodiments below. 1. A genomically stabilized population of pluripotent stem cells (PSCs) descended from an ancestral cell population. 2. The genomically stabilized population of embodiment 1, which is the progeny of at least 3 (e.g., 3) cell passages in culture from the ancestral cell population. 3. The genomically stabilized population of embodiment 1, which is the progeny of at least 4 (e.g., 4) cell passages in culture from the ancestral cell population. 4. The genomically stabilized population of embodiment 1, which is the progeny of at least 5 (e.g., 5) cell passages in culture from the ancestral cell population. 5. The genomically stabilized population of embodiment 1, which is the progeny of at least 6 (e.g., 6) cell passages in culture from the ancestral cell population. 6. The genomically stabilized population of embodiment 1, which is the progeny of at least 7 (e.g., 7) cell passages in culture from the ancestral cell population.7. The genomically stabilized population of embodiment 1, which is the progeny of at least 8 (e.g., 8) cell passages in culture from the ancestral cell population. 8. The genomically stabilized population of embodiment 1, which is the progeny of at least 9 (e.g., 9) cell passages in culture from the ancestral cell population. 9. The genomically stabilized population of embodiment 1, which is the progeny of at least 10 (e.g., 10) cell passages in culture from the ancestral cell population. 10. The genomically stabilized population of embodiment 1, which is the progeny of at least 11 (e.g., 11) cell passages in culture from the ancestral cell population. 11. The genomically stabilized population of embodiment 1, which is the progeny of at least 12 (e.g., 12) cell passages in culture from the ancestral cell population. 12. The genomically stabilized population of embodiment 1, which is the progeny of at least 13 (e.g., 13) cell passages in culture from the ancestral cell population. 13. The genomically stabilized population of embodiment 1, which is the progeny of at least 14 (e.g., 14) cell passages in culture from the ancestral cell population. 14. The genomically stabilized population of embodiment 1, which is the progeny of at least 15 (e.g., 15) cell passages in culture from the ancestral cell population. 15. The genomically stabilized population of embodiment 1, which is the progeny of at least 16 (e.g., 16) cell passages in culture from the ancestral cell population. 16. The genomically stabilized population of embodiment 1, which is the progeny of at least 17 (e.g., 17) cell passages in culture from the ancestral cell population. 17. The genomically stabilized population of embodiment 1, which is the progeny of at least 18 (e.g., 18) cell passages in culture from the ancestral cell population. 18. The genomically stabilized population of embodiment 1, which is the progeny of at least 19 (e.g., 19) cell passages in culture from the ancestral cell population. 19. The genomically stabilized population of embodiment 1, which is the progeny of at least 20 (e.g., 20) cell passages in culture from the ancestral cell population. 20. The genomically stabilized population of embodiment 1, which is the progeny of at least 21 (e.g., 21) cell passages in culture from the ancestral cell population. 21. The genomically stabilized population of embodiment 1, which is the progeny of at least 22 (e.g., 22) cell passages in culture from the ancestral cell population. 22. The genomically stabilized population of embodiment 1, which is the progeny of at least 23 (e.g., 23) cell passages in culture from the ancestral cell population. 23. The genomically stabilized population of embodiment 1, which is the progeny of at least 24 (e.g., 24) cell passages in culture from the ancestral cell population. 24. The genomically stabilized population of embodiment 1, which is the progeny of at least 25 (e.g., 25) cell passages in culture from the ancestral cell population. 25. The genomically stabilized population of any one of embodiments 1 to 18, which is the progeny of up to 20 passages in culture from the ancestral cell population.26. The genomically stabilized population of any one of embodiments 1 to 23, which is the progeny of up to 25 passages in culture from the ancestral cell population. 27. The genomically stabilized population of any one of embodiments 1 to 24, which is the progeny of up to 30 passages in culture from the ancestral cell population. 28. The genomically stabilized population of any one of embodiments 1 to 24, which is the progeny of up to 40 passages in culture from the ancestral cell population. 29. The genomically stabilized population of any one of embodiments 1 to 24, which is the progeny of up to 50 passages in culture from the ancestral cell population. 30. The genomically stabilized population of any one of embodiments 1 to 29, wherein at least half the passages from the ancestral cell population are clump passages. 31. The genomically stabilized population of any one of embodiments 1 to 30, wherein at least 60% of the passages from the ancestral cell population are clump passages. 32. The genomically stabilized population of any one of embodiments 1 to 31, wherein at least 70% of the passages from the ancestral cell population are clump passages. 33. The genomically stabilized population of any one of embodiments 1 to 32, wherein at least 75% of the passages from the ancestral cell population are clump passages. 34. The genomically stabilized population of any one of embodiments 1 to 33, wherein at least 80% of the passages from the ancestral cell population are clump passages. 35. The genomically stabilized population of any one of embodiments 1 to 34, wherein at least 85% of the passages from the ancestral cell population are clump passages. 36. The genomically stabilized population of any one of embodiments 1 to 35, wherein at least 90% of the passages from the ancestral cell population are clump passages. 37. The genomically stabilized population of any one of embodiments 1 to 36, wherein at least 95% of the passages from the ancestral cell population are clump passages. 38. The genomically stabilized population of any one of embodiments 1 to 37, wherein 100% of the passages from the ancestral cell population are clump passages. 39. The genomically stabilized population of any one of embodiments 30 to 38, wherein the clump passages have been performed in the presence of EDTA. 40. The genomically stabilized population of embodiment 39, wherein the clump passages have been performed by incubating a cell culture with 0.4-0.6 mM (e.g., 0.5 mM) EDTA. 41. The genomically stabilized population of embodiment 39 or embodiment 40, wherein the clump passages have been performed by incubating a cell culture with EDTA at a temperature below 40°C (e.g., below 40°C and optionally at least 15°C, or below 37°C and optionally at least 15°C). 42. The genomically stabilized population of any one of embodiments 39 to 41, wherein the clump passages have been performed by incubating a cell culture with EDTA at room temperature (e.g., at a temperature of 19°C-23°C).43. The genomically stabilized population of any one of embodiments 39 to 42, wherein the clump passages have been performed by incubating a cell culture with EDTA for 3- 50 minutes (e.g., for 5-50 minutes, 7-20 minutes or 30-45 minutes). 44. The genomically stabilized population of any one of embodiments 39 to 42, wherein the clump passages have been performed by incubating a cell culture with EDTA for 5- 25 minutes (e.g., for 7-20 minutes). 45. The genomically stabilized population of embodiment 44, wherein the clump passages have been performed by incubating a cell culture with EDTA for 7-20 minutes. 46. The genomically stabilized population of embodiment 44, wherein the clump passages have been performed by incubating a cell culture with EDTA for no more than 7 minutes (e.g., 7 minutes, 6 minutes, or 5 minutes). 47. The genomically stabilized population of embodiment 44, wherein the clump passages have been performed by incubating a cell culture with EDTA for 8-11 minutes. 48. The genomically stabilized population of embodiment 44, wherein the clump passages have been performed by incubating a cell culture with EDTA for 8-15 minutes. 49. The genomically stabilized population of embodiment 44, wherein the clump passages have been performed by incubating a cell culture with EDTA for 8-20 minutes. 50. The genomically stabilized population of any one of embodiments 39 to 42, wherein the clump passages have been performed by incubating a cell culture with EDTA for 25-50 minutes (e.g., for 30-45 minutes). 51. The genomically stabilized population of embodiment 50, wherein the clump passages have been performed by incubating a cell culture with EDTA for 30-45 minutes. 52. The genomically stabilized population of embodiment 50, wherein the clump passages have been performed by incubating a cell culture with EDTA for 25-35 minutes. 53. The genomically stabilized population of embodiment 50, wherein the clump passages have been performed by incubating a cell culture with EDTA for 30-40 minutes. 54. The genomically stabilized population of embodiment 50, wherein the clump passages have been performed by incubating a cell culture with EDTA for 35-45 minutes. 55. The genomically stabilized population of embodiment 50, wherein the clump passages have been performed by incubating a cell culture with EDTA for 40-50 minutes. 56. The genomically stabilized population of any one of embodiments 30 to 55, wherein the clump passages have been performed in the absence of a protease treatment, optionally in the absence of any exogenous enzymatic treatment. 57. The genomically stabilized population of any one of embodiments 1 to 56, wherein at least half the passages from the ancestral population are performed with a medium comprising one or more supplements, e.g., one or more cell protection supplements.58. The genomically stabilized population of any one of embodiments 1 to 57, wherein at least 60% of the passages from the ancestral population are performed with a medium comprising one or more supplements, e.g., one or more cell protection supplements. 59. The genomically stabilized population of any one of embodiments 1 to 58, wherein at least 70% of the passages from the ancestral population are performed with a medium comprising one or more supplements, e.g., one or more cell protection supplements. 60. The genomically stabilized population of any one of embodiments 1 to 59, wherein at least 75% of the passages from the ancestral population are performed with a medium comprising one or more supplements, e.g., one or more cell protection supplements. 61. The genomically stabilized population of any one of embodiments 1 to 60, wherein at least 80% of the passages from the ancestral population are performed with a medium comprising one or more supplements, e.g., one or more cell protection supplements. 62. The genomically stabilized population of any one of embodiments 1 to 61, wherein at least 85% of the passages from the ancestral population are performed with a medium comprising one or more supplements, e.g., one or more cell protection supplements. 63. The genomically stabilized population of any one of embodiments 1 to 62, wherein at least 90% of the passages from the ancestral population are performed with a medium comprising one or more supplements, e.g., one or more cell protection supplements. 64. The genomically stabilized population of any one of embodiments 1 to 63, wherein at least 95% of the passages from the ancestral population are performed with a medium comprising one or more supplements, e.g., one or more cell protection supplements. 65. The genomically stabilized population of any one of embodiments 1 to 64, wherein 100% of the passages from the ancestral population are performed with a medium comprising one or more supplements, e.g., one or more cell protection supplements. 66. The genomically stabilized population of any one of embodiments 57 to 65, wherein the one or more supplements comprise one or more ROCK inhibitors. 67. The genomically stabilized population of embodiment 66, wherein the one or more ROCK inhibitors comprise Y-27632. 68. The genomically stabilized population of embodiment 66 or embodiment 67, wherein the one or more ROCK inhibitors comprise chroman 1. 69. The genomically stabilized population of any one of embodiments 57 to 68, wherein the one or more supplements comprises a supplement cocktail, e.g., a cell protection supplement cocktail. 70. The genomically stabilized population of embodiment 69, wherein the supplement cocktail comprises CEPT (chroman 1, emricasan, polyamines, and trans-ISRIB) cocktail.71. The genomically stabilized population of any one of embodiments 57 to 70, wherein the medium comprising one or more supplements has been exchanged 18 to 30 hours (e.g., 24 hours) after passaging. 72. The genomically stabilized population of any one of embodiments 1 to 71, wherein at least half the passages from the ancestral population are performed with a medium comprising fibroblast growth factor 2 (FGF2) (e.g., heat-stabilized FGF2), basic fibroblast growth factor (e.g., rh bFGF), transforming growth factor beta (e.g., rh TGFβ), or a combination thereof. 73. The genomically stabilized population of any one of embodiments 1 to 72, wherein at least 60% of the passages from the ancestral population are performed with a medium comprising fibroblast growth factor 2 (FGF2) (e.g., heat-stabilized FGF2), basic fibroblast growth factor (e.g., rh bFGF), transforming growth factor beta (e.g., rh TGFβ), or a combination thereof. 74. The genomically stabilized population of any one of embodiments 1 to 73, wherein at least 70% of the passages from the ancestral population are performed with a medium comprising fibroblast growth factor 2 (FGF2) (e.g., heat-stabilized FGF2), basic fibroblast growth factor (e.g., rh bFGF), transforming growth factor beta (e.g., rh TGFβ), or a combination thereof. 75. The genomically stabilized population of any one of embodiments 1 to 74, wherein at least 75% of the passages from the ancestral population are performed with a medium comprising fibroblast growth factor 2 (FGF2) (e.g., heat-stabilized FGF2), basic fibroblast growth factor (e.g., rh bFGF), transforming growth factor beta (e.g., rh TGFβ), or a combination thereof. 76. The genomically stabilized population of any one of embodiments 1 to 75, wherein at least 80% of the passages from the ancestral population are performed with a medium comprising fibroblast growth factor 2 (FGF2) (e.g., heat-stabilized FGF2), basic fibroblast growth factor (e.g., rh bFGF), transforming growth factor beta (e.g., rh TGFβ), or a combination thereof. 77. The genomically stabilized population of any one of embodiments 1 to 76, wherein at least 85% of the passages from the ancestral population are performed with a medium comprising fibroblast growth factor 2 (FGF2) (e.g., heat-stabilized FGF2), basic fibroblast growth factor (e.g., rh bFGF), transforming growth factor beta (e.g., rh TGFβ), or a combination thereof. 78. The genomically stabilized population of any one of embodiments 1 to 77, wherein at least 90% of the passages from the ancestral population are performed with a medium comprising fibroblast growth factor 2 (FGF2) (e.g., heat-stabilized FGF2), basic fibroblast growth factor (e.g., rh bFGF), transforming growth factor beta (e.g., rh TGFβ), or a combination thereof.79. The genomically stabilized population of any one of embodiments 1 to 78, wherein at least 95% of the passages from the ancestral population are performed with a medium comprising fibroblast growth factor 2 (FGF2) (e.g., heat-stabilized FGF2), basic fibroblast growth factor (e.g., rh bFGF), transforming growth factor beta (e.g., rh TGFβ), or a combination thereof. 80. The genomically stabilized population of any one of embodiments 1 to 79, wherein 100% of the passages from the ancestral population are performed with a medium comprising fibroblast growth factor 2 (FGF2) (e.g., heat-stabilized FGF2), basic fibroblast growth factor (e.g., rh bFGF), transforming growth factor beta (e.g., rh TGFβ), or a combination thereof. 81. The genomically stabilized population of any one of embodiments 72 to 80, wherein the medium comprises FGF2. 82. The genomically stabilized population of any one of embodiments 72 to 81, wherein the medium comprises bFGF (e.g., rh bFGF). 83. The genomically stabilized population of any one of embodiments 72 to 82, wherein the medium comprises TGFβ (e.g., rh TGFβ). 84. The genomically stabilized population of any one of embodiments 72 to 82, wherein the medium comprises FGF2, TGF-β1, insulin, human serum albumin, a buffer, LiCl, L- ascorbic acid, or a combination thereof. 85. The genomically stabilized population of any one of embodiments 72 to 82, wherein the medium comprises FGF2, TGF-β1 or Activin A, insulin or insulin-like growth factor 1 (IGF-1), a buffer, antioxidants, or a combination thereof. 86. The genomically stabilized population of any one of embodiments 72 to 82, wherein the medium comprises FGF2, TGF-β1 or Nodal, insulin, transferrin, L-ascorbic acid 2- phosphate, sodium selenite, sodium bicarbonate, or a combination thereof. 87. The genomically stabilized population of any one of embodiments 72 to 82, wherein the medium comprises FGF2, TGF-β1, insulin, human serum albumin, transferrin, LiCl, L-ascorbic acid, or a combination thereof. 88. The genomically stabilized population of any one of embodiments 1 to 87, wherein at least half the passages from the ancestral population are performed with a medium comprising CTS-E8, eTeSR™, mTeSR™ Plus, mTeSR™ 1, StemFit®, xCellerate™, or iPS Brew XF™ medium. 89. The genomically stabilized population of any one of embodiments 1 to 88, wherein at least 60% of the passages from the ancestral population are performed with a medium comprising CTS-E8, eTeSR™, mTeSR™ Plus, mTeSR™ 1, StemFit®, xCellerate™, or iPS Brew XF™ medium. 90. The genomically stabilized population of any one of embodiments 1 to 89, wherein at least 70% of the passages from the ancestral population are performed with amedium comprising CTS-E8, eTeSR™, mTeSR™ Plus, mTeSR™ 1, StemFit®, xCellerate™, or iPS Brew XF™ medium. 91. The genomically stabilized population of any one of embodiments 1 to 90, wherein at least 75% of the passages from the ancestral population are performed with a medium comprising CTS-E8, eTeSR™, mTeSR™ Plus, mTeSR™ 1, StemFit®, xCellerate™, or iPS Brew XF™ medium. 92. The genomically stabilized population of any one of embodiments 1 to 91, wherein at least 80% of the passages from the ancestral population are performed with a medium comprising CTS-E8, eTeSR™, mTeSR™ Plus, mTeSR™ 1, StemFit®, xCellerate™, or iPS Brew XF™ medium. 93. The genomically stabilized population of any one of embodiments 1 to 92, wherein at least 85% of the passages from the ancestral population are performed with a medium comprising CTS-E8, eTeSR™, mTeSR™ Plus, mTeSR™ 1, StemFit®, xCellerate™, or iPS Brew XF™ medium. 94. The genomically stabilized population of any one of embodiments 1 to 93, wherein at least 90% of the passages from the ancestral population are performed with a medium comprising CTS-E8, eTeSR™, mTeSR™ Plus, mTeSR™ 1, StemFit®, xCellerate™, or iPS Brew XF™ medium. 95. The genomically stabilized population of any one of embodiments 1 to 94, wherein at least 95% of the passages from the ancestral population are performed with a medium comprising CTS-E8, eTeSR™, mTeSR™ Plus, mTeSR™ 1, StemFit®, xCellerate™, or iPS Brew XF™ medium. 96. The genomically stabilized population of any one of embodiments 1 to 95, wherein 100% of the passages from the ancestral population are performed with a medium comprising CTS-E8, eTeSR™, mTeSR™ Plus, mTeSR™ 1, StemFit®, xCellerate™, or iPS Brew XF™ medium. 97. The genomically stabilized population of any one of embodiments 84 to 96, wherein the medium comprises CTS-E8 medium. 98. The genomically stabilized population of any one of embodiments 84 to 96, wherein the medium comprises eTeSR™ medium. 99. The genomically stabilized population of any one of embodiments 84 to 96, wherein the medium comprises mTeSR™ Plus medium. 100. The genomically stabilized population of any one of embodiments 84 to 96, wherein the medium comprises mTeSR™ 1 medium. 101. The genomically stabilized population of any one of embodiments 84 to 96, wherein the medium comprises StemFit® medium. 102. The genomically stabilized population of any one of embodiments 84 to 96, wherein the medium comprises xCellerate™ medium.103. The genomically stabilized population of any one of embodiments 84 to 96, wherein the medium comprises iPS Brew XF™ medium. 104. The genomically stabilized population of any one of embodiments 1 to 103, which is the progeny of at least 2 expansions in culture. 105. The genomically stabilized population of any one of embodiments 1 to 104, which is the progeny of at least 3 expansions in culture. 106. The genomically stabilized population of any one of embodiments 1 to 105, which is the progeny of at least 4 expansions in culture. 107. The genomically stabilized population of any one of embodiments 1 to 106, which is the progeny of at least 5 expansions in culture. 108. The genomically stabilized population of any one of embodiments 104 to 107, wherein a majority of phases of a majority of expansions have been performed in the presence of at least one laminin moiety. 109. The genomically stabilized population of any one of embodiments 104 to 107, wherein a majority of phases of all expansions have been performed in the presence of at least one laminin moiety. 110. The genomically stabilized population of any one of embodiments 104 to 107, wherein all phases of a majority of expansions have been performed in the presence of at least one laminin moiety. 111. The genomically stabilized population of any one of embodiments 104 to 107, wherein all phases of all expansions have been performed in the presence of at least one laminin moiety. 112. The genomically stabilized population of any one of embodiments 108 to 111, wherein the at least one laminin moiety comprises a full-length laminin and / or a laminin fragment. 113. The genomically stabilized population of any one of embodiments 108 to 112, wherein the at least one laminin moiety is a trimer comprising a laminin alpha, a laminin beta and a laminin gamma. 114. The genomically stabilized population of embodiment 113, wherein the laminin alpha comprises an amino acid sequence having at least 77% sequence identity to the amino acid sequence of SEQ ID NO:4. 115. The genomically stabilized population of embodiment 113, wherein the laminin alpha comprises an amino acid sequence having at least 77% sequence identity to the amino acid sequence of SEQ ID NO:5. 116. The genomically stabilized population of embodiment 113, wherein the laminin alpha comprises an amino acid sequence having at least 77% sequence identity to the amino acid sequence of SEQ ID NO:6.117. The genomically stabilized population of any one of embodiments 113 to 116, wherein the laminin beta comprises an amino acid sequence having at least 93% sequence identity to the amino acid sequence of SEQ ID NO:15 and includes the amino acid sequence of SEQ ID NO:17. 118. The genomically stabilized population of any one of embodiments 113 to 116, wherein the laminin beta comprises an amino acid sequence having at least 93% sequence identity to the amino acid sequence of SEQ ID NO:16 and includes the amino acid sequence of SEQ ID NO:18. 119. The genomically stabilized population of any one of embodiments 113 to 118, wherein the laminin gamma comprises an amino acid sequence having at least 89% sequence identity to the amino acid sequence of SEQ ID NO:27 and includes the amino acid sequence of SEQ ID NO:29. 120. The genomically stabilized population of any one of embodiments 113 to 118, wherein the laminin gamma comprises an amino acid sequence having at least 89% sequence identity to the amino acid sequence of SEQ ID NO:28 and includes the amino acid sequence of SEQ ID NO:30. 121. The genomically stabilized population of any one of embodiments 113 to 120, wherein the laminin alpha comprises an amino acid sequence having at least 79% sequence identity to the amino acid sequence of SEQ ID NO:31. 122. The genomically stabilized population of any one of embodiments 113 to 120, wherein the laminin alpha comprises an amino acid sequence having at least 79% sequence identity to the amino acid sequence of SEQ ID NO:32. 123. The genomically stabilized population of any one of embodiments 113 to 120, wherein the laminin alpha comprises an amino acid sequence having at least 79% sequence identity to the amino acid sequence of SEQ ID NO:33. 124. The genomically stabilized population of any one of embodiments 113 to 123, wherein the laminin beta comprises an amino acid sequence having at least 88% sequence identity to the amino acid sequence of SEQ ID NO:36. 125. The genomically stabilized population of any one of embodiments 113 to 123, wherein the laminin beta comprises an amino acid sequence having at least 88% sequence identity to the amino acid sequence of SEQ ID NO: 37. 126. The genomically stabilized population of any one of embodiments 113 to 125, wherein the laminin gamma comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO:38. 127. The genomically stabilized population of any one of embodiments 113 to 125, wherein the laminin gamma comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO:39.128. The genomically stabilized population of any one of embodiments 108 to 127, wherein the at least one laminin moiety comprises LN521. 129. The genomically stabilized population of any one of embodiments 108 to 128, wherein the at least one laminin moiety comprises LN-511-E8. 130. The genomically stabilized population of any one of embodiments 104 to 129, wherein a majority of (optionally all) phases of a majority of (optionally all) expansions have been performed in the absence of a vitronectin (e.g., VTN-1 and / or VTN-2). 131. The genomically stabilized population of any one of embodiments 104 to 130, wherein a majority of (optionally all) phases of a majority of (optionally all) expansions have been performed in the absence of a cadherin (e.g., e-cadherin). 132. The genomically stabilized population of any one of embodiments 104 to 131, wherein a majority of (optionally all) phases of a majority of (optionally all) expansions have been performed in the absence of a cell feeder layer. 133. The genomically stabilized population of any one of embodiments 104to 132, wherein a majority of (optionally all) phases of a majority of (optionally all) expansions have been performed on an adherent surface. 134. The genomically stabilized population of any one of embodiments 104 to 133, wherein a majority of (optionally all) phases of a majority of (optionally all) expansions have been performed on a surface treated for increased PSC adherence, optionally wherein the surface is treated for increased hydrophilicity. 135. The genomically stabilized population of any one of embodiments 104 to 134, wherein a majority of (optionally all) phases of a majority of (optionally all) expansions have been performed on a surface comprising means for increased PSC adherence. 136. The genomically stabilized population of any one of embodiments 104 to 135, wherein a majority of (optionally all) phases of a majority of (optionally all) expansions have been performed on a tissue culture treated vessel surface, optionally wherein the tissue culture treated vessel surface is (a) a ThermoFisher Nunclon™ Delta-treated surface, (b) an Azer Scientific tissue culture treated surface, (c) an equivalent of (a) and / or (b), or (d) any combination of (a), (b) and (c). 137. The genomically stabilized population of any one of embodiments 1 to 136, which is the product of at least one round of cryopreservation and reactivation. 138. The genomically stabilized population of any one of embodiments 1 to 137, which is the product of at least two rounds of cryopreservation and reactivation. 139. The genomically stabilized population of any one of embodiments 1 to 138, which is the product of at least three rounds of cryopreservation and reactivation. 140. The genomically stabilized population of any of embodiments 1 to 139, in which (a) the prevalence of BCOR SNP1 is less than 1% in the population and / or (b) (i) the populationis a male cell population and the BCOR SNP1 VAF is less than 1% or (ii) the population is a female cell population and the BCOR SNP1 VAF is less than 1%. 141. The genomically stabilized population of any of embodiments 1 to 140, in which (a) the prevalence of BCOR SNP1 is less than 0.5% in the population and / or (b) (i) the population is a male cell population and the BCOR SNP1 VAF is less than 0.5% or (ii) the population is a female cell population and the BCOR SNP1 VAF is less than 0.5%. 142. The genomically stabilized population of any of embodiments 1 to 141, in which (a) the prevalence of BCOR SNP1 is less than 0.1% in the population and / or (b) (i) the population is a male cell population and the BCOR SNP1 VAF is less than 0.1% or (ii) the population is a female cell population and the BCOR SNP1 VAF is less than 0.1%. 143. The genomically stabilized population of any of embodiments 1 to 142, in which (a) the prevalence of BCOR SNP1 is less than 0.05% in the population and / or (b) (i) the population is a male cell population and the BCOR SNP1 VAF is less than 0.05% or (ii) the population is a female cell population and the BCOR SNP1 VAF is less than 0.05%. 144. The genomically stabilized population of any of embodiments 1 to 143, in which (a) the prevalence of BCOR SNP1 is less than 0.01% in the population and / or (b) (i) the population is a male cell population and the BCOR SNP1 VAF is less than 0.01% or (ii) the population is a female cell population and the BCOR SNP1 VAF is less than 0.01%. 145. The genomically stabilized population of any of embodiments 1 to 144, in which (a) the prevalence of BCOR SNP2 is less than 1% in the population and / or (b) (i) the population is a male cell population and the BCOR SNP2 VAF is less than 1% or (ii) the population is a female cell population and the BCOR SNP2 VAF is less than 1%. 146. The genomically stabilized population of any of embodiments 1 to 145, in which (a) the prevalence of BCOR SNP2 is less than 0.5% in the population and / or (b) (i) the population is a male cell population and the BCOR SNP2 VAF is less than 0.5% or (ii) the population is a female cell population and the BCOR SNP2 VAF is less than 0.5%. 147. The genomically stabilized population of any of embodiments 1 to 146, in which (a) the prevalence of BCOR SNP2 is less than 0.1% in the population and / or (b) (i) the population is a male cell population and the BCOR SNP2 VAF is less than 0.1% or (ii) the population is a female cell population and the BCOR SNP2 VAF is less than 0.1%. 148. The genomically stabilized population of any of embodiments 1 to 147, in which (a) the prevalence of BCOR SNP2 is less than 0.05% in the population and / or (b) (i) the population is a male cell population and the BCOR SNP2 VAF is less than 0.05% or (ii) the population is a female cell population and the BCOR SNP2 VAF is less than 0.05%. 149. The genomically stabilized population of any of embodiments 1 to 148 in which (a) the prevalence of BCOR SNP2 is less than 0.01% in the population and / or (b) (i) the population is a male cell population and the BCOR SNP2 VAF is less than 0.01% or (ii) the population is a female cell population and the BCOR SNP2 VAF is less than 0.01%.150. The genomically stabilized population of any of embodiments 1 to 149, in which the prevalence of RARA SNP is less than 1%. 151. The genomically stabilized population of any of embodiments 1 to 150, in which the prevalence of RARA SNP is less than 0.5%. 152. The genomically stabilized population of any of embodiments 1 to 151, in which the prevalence of RARA SNP is less than 0.1%. 153. The genomically stabilized population of any of embodiments 1 to 152, in which the prevalence of RARA SNP is less than 0.05%. 154. The genomically stabilized population of any of embodiments 1 to 153, in which the prevalence of RARA SNP is less than 0.01%. 155. The genomically stabilized population of any one of embodiments 1 to 154, which is a population of induced pluripotent stem cells (iPSCs). 156. The genomically stabilized population of embodiment 155, wherein the iPSCs are of a hematopoietic origin. 157. The genomically stabilized population of embodiment 155 or embodiment 156, wherein the iPSCs are the product of reprogramming a hematopoietic cell, e.g., using any combination of the reprogramming factors, alphavirus vectors, reprogramming methods described in WO / 2022 / 204567, the contents of which are incorporated by reference herein in their entireties. 158. The genomically stabilized population of any one of embodiments 1 to 154, which is a population of embryonic stem cells ESCs. 159. The genomically stabilized population of any one of embodiments 1 to 158, which is a human cell population. 160. The genomically stabilized population of any one of embodiments 1 to 159, which is in the form of an in vitro cell culture. 161. The genomically stabilized population of embodiment 160, wherein the cell culture is an adherent cell culture. 162. The genomically stabilized population of embodiment 160 or embodiment 161, wherein the cell culture comprises at least one laminin moiety. 163. The genomically stabilized population of any one of embodiments 1 to 159, which is cryopreserved. 164. The genomically stabilized population of embodiment 163, which is in a cryopreservation solution. 165. The genomically stabilized population of embodiment 163 or embodiment 164, which is in a cryopreservation vial. 166. The genomically stabilized population of embodiment 165, wherein the vial is part of a cell bank.167. A method of producing a seed cell bank comprising a genomically stabilized population of PSCs, comprising: (a) expanding one or more cells of an ancestral cell population in culture in the presence of a laminin moiety under conditions in which a genomically stabilized population of PSCs is produced; (b) dispensing genomically stabilized population of PSCs produced in step (a) into cryopreservation containers; and (c) subjecting the cryopreservation containers to cryopreservation conditions, thereby producing a seed cell bank. 168. A method of producing a seed cell bank comprising a genomically stabilized population of PSCs, comprising: (a) expanding one or more cells of an ancestral cell population in culture in the presence of one or more supplements, e.g., one or more cell protection supplements, under conditions in which a genomically stabilized population of PSCs is produced; (b) dispensing genomically stabilized population of PSCs produced in step (a) into cryopreservation containers; and (c) subjecting the cryopreservation containers to cryopreservation conditions, thereby producing a seed cell bank. 169. The method of embodiment 168, wherein the one or more supplements comprise one or more ROCK inhibitors. 170. The method of embodiment 169, wherein the one or more ROCK inhibitors comprise Y-27632. 171. The method of embodiment 169 or embodiment 170, wherein the one or more ROCK inhibitors comprise chroman 1. 172. The method of any one of embodiments 168 to 171, wherein the one or more supplements comprises a supplement cocktail, e.g., a cell protection supplement cocktail. 173. The method of embodiment 172, wherein the supplement cocktail comprises CEPT (chroman 1, emricasan, polyamines, and trans-ISRIB) cocktail. 174. The method of any one of embodiments 168 to 173, wherein step (a) is performed in the presence of a laminin moiety. 175. The method of any one of embodiments 167 to 174, wherein step (a) comprises at least 2 (e.g., 2) passages of the ancestral cell population and its progeny. 176. The method of any one of embodiments 167 to 174, wherein step (a) comprises at least 3 (e.g., 3) passages of the ancestral cell population and its progeny.177. The method of any one of embodiments 167 to 174, wherein step (a) comprises at least 4 (e.g., 4) passages of the ancestral cell population and its progeny. 178. The method of any one of embodiments 167 to 174, wherein step (a) comprises at least 5 (e.g., 5) passages of the ancestral cell population and its progeny. 179. The method of any one of embodiments 167 to 178, wherein step (a) comprises up to 6 or up to 7 passages of the ancestral cell population and its progeny. 180. The method of any one of embodiments 167 to 179, wherein at least half the passages from the ancestral cell population are clump passages. 181. The method of any one of embodiments 167 to 180, wherein at least 60% of the passages from the ancestral cell population are clump passages. 182. The method of any one of embodiments 167 to 181, wherein at least 70% of the passages from the ancestral cell population are clump passages. 183. The method of any one of embodiments 167 to 182, wherein at least 80% of the passages from the ancestral cell population are clump passages. 184. The method of any one of embodiments 167 to 183, wherein at least 90% of the passages from the ancestral cell population are clump passages. 185. The method of any one of embodiments 167 to 184, wherein 100% of the passages from the ancestral cell population are clump passages. 186. The method of any one of embodiments 180 to 185, wherein the clump passages are performed in the presence of EDTA. 187. The method of embodiment 186, wherein the clump passages are performed by incubating a cell culture with 0.4-0.6 mM (e.g., 0.5 mM) EDTA. 188. The method of embodiment 186 or embodiment 187, wherein the clump passages are performed by incubating a cell culture with EDTA at a temperature below 40°C (e.g., below 40°C and optionally at least 15°C, or below 37°C and optionally at least 15°C). 189. The method of any one of embodiments 186to 188, wherein the clump passages are performed by incubating a cell culture with EDTA at room temperature (e.g., at a temperature of 19°C-23°C). 190. The method of any one of embodiments 186 to 189, wherein the clump passages are performed by incubating a cell culture with EDTA for 5-50 minutes (e.g., for 7-20 minutes or 30-45 minutes). 191. The method of any one of embodiments 186 to 189, wherein the clump passages are performed by incubating a cell culture with EDTA for 5-25 minutes (e.g., for 7-20 minutes). 192. The method of embodiment 191, wherein the clump passages are performed by incubating a cell culture with EDTA for no more than 7 minutes (e.g., 7 minutes, 6 minutes, or 5 minutes).193. The method of embodiment 191, wherein the clump passages are performed by incubating a cell culture with EDTA for 7-20 minutes. 194. The method of embodiment 191, wherein the clump passages are performed by incubating a cell culture with EDTA for 8-11 minutes. 195. The method of embodiment 191, wherein the clump passages are performed by incubating a cell culture with EDTA for 8-15 minutes. 196. The method of embodiment 191, wherein the clump passages are performed by incubating a cell culture with EDTA for 8-20 minutes. 197. The method of any one of embodiments 186 to 189, wherein the clump passages are performed by incubating a cell culture with EDTA for 25-50 minutes (e.g., for 30- 45 minutes). 198. The method of embodiment 197, wherein the clump passages are performed by incubating a cell culture with EDTA for 30-45 minutes. 199. The method of embodiment 197, wherein the clump passages are performed by incubating a cell culture with EDTA for 25-35 minutes. 200. The method of embodiment 197, wherein the clump passages are performed by incubating a cell culture with EDTA for 30-40 minutes. 201. The method of embodiment 197, wherein the clump passages are performed by incubating a cell culture with EDTA for 35-45 minutes. 202. The method of embodiment 197, wherein the clump passages are performed by incubating a cell culture with EDTA for 40-50 minutes. 203. The method of any one of embodiments 180 to 202, wherein the clump passages are performed in the absence of a protease treatment, optionally in the absence of any exogenous enzymatic treatment. 204. The method of any one of embodiments 167 to 203, wherein at least half the passages from the ancestral population are performed with a medium comprising one or more supplements, e.g., one or more cell protection supplements. 205. The method of any one of embodiments 167 to 204, wherein at least 60% of the passages from the ancestral population are performed with a medium comprising one or more supplements, e.g., one or more cell protection supplements. 206. The method of any one of embodiments 167 to 205, wherein at least 70% of the passages from the ancestral population are performed with a medium comprising one or more supplements, e.g., one or more cell protection supplements. 207. The method of any one of embodiments 167 to 206, wherein at least 80% of the passages from the ancestral population are performed with a medium comprising one or more supplements, e.g., one or more cell protection supplements.208. The method of any one of embodiments 167 to 207, wherein at least 90% of the passages from the ancestral population are performed with a medium comprising one or more supplements, e.g., one or more cell protection supplements. 209. The method of any one of embodiments 167 to 208, wherein 100% of the passages from the ancestral population are performed with a medium comprising one or more supplements, e.g., one or more cell protection supplements. 210. The method of any one of embodiments 204 to 209, wherein the one or more supplements comprise one or more ROCK inhibitors. 211. The method of embodiment 210, wherein the one or more ROCK inhibitors comprise Y-27632. 212. The method of embodiment 210 or embodiment 211, wherein the one or more ROCK inhibitors comprise chroman 1. 213. The method of any one of embodiments 204 to 212, wherein the one or more supplements comprises a supplement cocktail, e.g., a cell protection supplement cocktail. 214. The method of embodiment 213, wherein the supplement cocktail comprises CEPT (chroman 1, emricasan, polyamines, and trans-ISRIB) cocktail. 215. The method of any one of embodiments 180 to 214, wherein the seed cell bank is the progeny of at least one expansion in culture from the ancestral cell population. 216. The method of embodiment 215, wherein a majority of phases of the at least one expansion are performed in the presence of at least one laminin moiety. 217. The method of embodiment 215, wherein all phases of the at least one expansion are performed in the presence of at least one laminin moiety. 218. The method of any one of embodiments 216 to 217, wherein the at least one laminin moiety comprises a full-length laminin and / or a laminin fragment. 219. The method of any one of embodiments 216 to 218, wherein the at least one laminin moiety is a trimer comprising a laminin alpha, a laminin beta and a laminin gamma. 220. The method of embodiment 219, wherein the laminin alpha comprises an amino acid sequence having at least 77% sequence identity to the amino acid sequence of SEQ ID NO:4. 221. The method of embodiment 219, wherein the laminin alpha comprises an amino acid sequence having at least 77% sequence identity to the amino acid sequence of SEQ ID NO:5. 222. The method of embodiment 219, wherein the laminin alpha comprises an amino acid sequence having at least 77% sequence identity to the amino acid sequence of SEQ ID NO:6. 223. The method of any one of embodiments 219 to 222, wherein the laminin beta comprises an amino acid sequence having at least 93% sequence identity to the amino acid sequence of SEQ ID NO:15 and includes the amino acid sequence of SEQ ID NO:17.224. The method of any one of embodiments 219 to 222, wherein the laminin beta comprises an amino acid sequence having at least 93% sequence identity to the amino acid sequence of SEQ ID NO:16 and includes the amino acid sequence of SEQ ID NO:18. 225. The method of any one of embodiments 219 to 224, wherein the laminin gamma comprises an amino acid sequence having at least 89% sequence identity to the amino acid sequence of SEQ ID NO:27 and includes the amino acid sequence of SEQ ID NO:29. 226. The method of any one of embodiments 219 to 224, wherein the laminin gamma comprises an amino acid sequence having at least 89% sequence identity to the amino acid sequence of SEQ ID NO:28 and includes the amino acid sequence of SEQ ID NO:30. 227. The method of any one of embodiments 219 to 226, wherein the laminin alpha comprises an amino acid sequence having at least 79% sequence identity to the amino acid sequence of SEQ ID NO:31. 228. The method of any one of embodiments 219 to 226, wherein the laminin alpha comprises an amino acid sequence having at least 79% sequence identity to the amino acid sequence of SEQ ID NO:32. 229. The method of any one of embodiments 219 to 226, wherein the laminin alpha comprises an amino acid sequence having at least 79% sequence identity to the amino acid sequence of SEQ ID NO:33. 230. The method of any one of embodiments 219 to 229, wherein the laminin beta comprises an amino acid sequence having at least 88% sequence identity to the amino acid sequence of SEQ ID NO:36. 231. The method of any one of embodiments 219 to 229, wherein the laminin beta comprises an amino acid sequence having at least 88% sequence identity to the amino acid sequence of SEQ ID NO: 37. 232. The method of any one of embodiments 219 to 231, wherein the laminin gamma comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO:38. 233. The method of any one of embodiments 219 to 231, wherein the laminin gamma comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO:39. 234. The method of any one of embodiments 216 to 233, wherein the at least one laminin moiety comprises LN521. 235. The method of any one of embodiments 216 to 234, wherein the laminin moiety comprises LN-511-E8. 236. The method of any one of embodiments 215 to 235, wherein a majority of (optionally all) phases of the at least one expansion are performed in the absence of a vitronectin (e.g., in the absence of VTN-1 and / or VTN-2).237. The method of any one of embodiments 215 to 236, wherein a majority of (optionally all) phases of the at least one expansion are performed in the absence of a cadherin (e.g., in the absence of e-cadherin). 238. The method of any one of embodiments 215 to 236, wherein a majority of (optionally all) phases of the at least one expansion are performed on an adherent surface. 239. The method of any one of embodiments 215 to 238, wherein a majority of (optionally all) phases of the at least one expansion are performed on a surface treated for increased PSC adherence, optionally wherein the surface is treated for increased hydrophilicity. 240. The method of any one of embodiments 215 to 239, wherein a majority of (optionally all) phases of the at least one expansion are performed on a surface comprising means for increased PSC adherence. 241. The method of any one of embodiments 215 to 240, wherein a majority of (optionally all) phases of the at least one expansion are performed on a tissue culture treated vessel surface, optionally wherein the tissue culture treated vessel surface is (a) a ThermoFisher Nunclon™ Delta-treated surface, (b) an Azer Scientific tissue culture treated surface, (c) an equivalent of (a) and / or (b), or (d) any combination of (a), (b) and (c). 242. The method of any one of embodiments 167 to 241, wherein (a) the prevalence of BCOR SNP1 is less than 1% in the population of cells in the seed cell bank and / or (b) (i) population of cells in the seed cell bank is a male cell population and the BCOR SNP1 VAF is less than 1% or (ii) population of cells in the seed cell bank is a female cell population and the BCOR SNP1 VAF is less than 1%. 243. The method of any one of embodiments 167 to 242, wherein (a) the prevalence of BCOR SNP1 is less than 0.5% in the population of cells in the seed cell bank and / or (b) (i) population of cells in the seed cell bank is a male cell population and the BCOR SNP1 VAF is less than 0.5% or (ii) population of cells in the seed cell bank is a female cell population and the BCOR SNP1 VAF is less than 0.5%. 244. The method of any one of embodiments 167 to 243, wherein (a) the prevalence of BCOR SNP1 is less than 0.1% in the population of cells in the seed cell bank and / or (b) (i) population of cells in the seed cell bank is a male cell population and the BCOR SNP1 VAF is less than 0.1% or (ii) population of cells in the seed cell bank is a female cell population and the BCOR SNP1 VAF is less than 0.1%. 245. The method of any one of embodiments 167 to 244, wherein (a) the prevalence of BCOR SNP1 is less than 0.05% in the population of cells in the seed cell bank and / or (b) (i) population of cells in the seed cell bank is a male cell population and the BCOR SNP1 VAF is less than 0.05% or (ii) population of cells in the seed cell bank is a female cell population and the BCOR SNP1 VAF is less than 0.05%. 246. The method of any one of embodiments 167 to 245, wherein (a) the prevalence of BCOR SNP1 is less than 0.01% in the population of cells in the seed cell bank and / or (b) (i)population of cells in the seed cell bank is a male cell population and the BCOR SNP1 VAF is less than 0.01% or (ii) population of cells in the seed cell bank is a female cell population and the BCOR SNP1 VAF is less than 0.01%. 247. The method of any one of embodiments 167 to 246, wherein (a) the prevalence of BCOR SNP2 is less than 1% in the population of cells in the seed cell bank and / or (b) (i) population of cells in the seed cell bank is a male cell population and the BCOR SNP2 VAF is less than 1% or (ii) population of cells in the seed cell bank is a female cell population and the BCOR SNP2 VAF is less than 1%. 248. The method of any one of embodiments 167 to 247, wherein (a) the prevalence of BCOR SNP2 is less than 0.5% in the population of cells in the seed cell bank and / or (b) (i) population of cells in the seed cell bank is a male cell population and the BCOR SNP2 VAF is less than 0.5% or (ii) population of cells in the seed cell bank is a female cell population and the BCOR SNP2 VAF is less than 0.5%. 249. The method of any one of embodiments 167 to 248, wherein (a) the prevalence of BCOR SNP2 is less than 0.1% in the population of cells in the seed cell bank and / or (b) (i) population of cells in the seed cell bank is a male cell population and the BCOR SNP2 VAF is less than 0.1% or (ii) population of cells in the seed cell bank is a female cell population and the BCOR SNP2 VAF is less than 0.1%. 250. The method of any one of embodiments 167 to 249, wherein (a) the prevalence of BCOR SNP2 is less than 0.05% in the population of cells in the seed cell bank and / or (b) (i) population of cells in the seed cell bank is a male cell population and the BCOR SNP2 VAF is less than 0.05% or (ii) population of cells in the seed cell bank is a female cell population and the BCOR SNP2 VAF is less than 0.05%. 251. The method of any one of embodiments 167 to 250, wherein (a) the prevalence of BCOR SNP2 is less than 0.01% in the population of cells in the seed cell bank and / or (b) (i) population of cells in the seed cell bank is a male cell population and the BCOR SNP2 VAF is less than 0.01% or (ii) population of cells in the seed cell bank is a female cell population and the BCOR SNP2 VAF is less than 0.01%. 252. The method of any one of embodiments 167 to 251, wherein the prevalence of RARA SNP in cells of the seed cell bank is less than 1%. 253. The method of any one of embodiments 167 to 252, wherein the prevalence of RARA SNP in cells of the seed cell bank is less than 0.5%. 254. The method of any one of embodiments 134 to 253, wherein the prevalence of RARA SNP in cells of the seed cell bank is less than 0.1%. 255. The method of any one of embodiments 134 to 254, wherein the prevalence of RARA SNP in cells of the seed cell bank is less than 0.05%. 256. The method of any one of embodiments 134 to 255, wherein the prevalence of RARA SNP in cells of the seed cell bank is less than 0.01%.257. The method of any one of embodiments 134 to 256, wherein the ancestral cell population is a population of iPSCs. 258. A method of producing a master cell bank comprising a genomically stabilized population of PSCs, comprising: (a) expanding one or more cells of a seed cell bank in culture in the presence of a laminin moiety under conditions in which a genomically stabilized population of PSCs is produced; (b) dispensing genomically stabilized population of PSCs produced in step (a) into cryopreservation containers; and (c) subjecting the cryopreservation containers to cryopreservation conditions, thereby producing a master cell bank. 259. A method of producing a master cell bank comprising a genomically stabilized population of PSCs, comprising: (a) expanding one or more cells of a seed cell bank in culture in the presence of one or more supplements, e.g., one or more cell protection supplements, under conditions in which a genomically stabilized population of PSCs is produced; (b) dispensing genomically stabilized population of PSCs produced in step (a) into cryopreservation containers; and (c) subjecting the cryopreservation containers to cryopreservation conditions, thereby producing a master cell bank. 260. The method of embodiment 259, wherein the one or more supplements comprise one or more ROCK inhibitors. 261. The method of embodiment 260, wherein the one or more ROCK inhibitors comprise Y-27632. 262. The method of embodiment 260 or embodiment 261, wherein the one or more ROCK inhibitors comprise chroman 1. 263. The method of any one of embodiments 259 to 262, wherein the one or more supplements comprises a supplement cocktail, e.g., a cell protection supplement cocktail. 264. The method of embodiment 263, wherein the supplement cocktail comprises CEPT (chroman 1, emricasan, polyamines, and trans-ISRIB) cocktail. 265. The method of any one of embodiments 259 to 264, wherein step (a) is performed in the presence of a laminin moiety. 266. The method of any one of embodiments 258 to 265, wherein step (a) comprises at least 3 (e.g., 3) passages of the cell population of the seed cell bank and its progeny.267. The method of any one of embodiments 258 to 265, wherein step (a) comprises at least 4 (e.g., 4) passages of the cell population of the seed cell bank and its progeny. 268. The method of any one of embodiments 258 to 265, wherein step (a) comprises at least 5 (e.g., 5) passages of the cell population of the seed cell bank and its progeny. 269. The method of any one of embodiments 258 to 268, wherein step (a) comprises up to 6 or up to 7 passages of the cell population of the seed cell bank and its progeny. 270. The method of any one of embodiments 258 to 269, wherein at least half the passages from the cell population of the seed cell bank are clump passages. 271. The method of any one of embodiments 258 to 270, wherein at least 60% passages from the cell population of the seed cell bank are clump passages. 272. The method of any one of embodiments 258 to 271, wherein at least 70% passages from the cell population of the seed cell bank are clump passages. 273. The method of any one of embodiments 258 to 272, wherein at least 80% passages from the cell population of the seed cell bank are clump passages. 274. The method of any one of embodiments 258 to 273, wherein at least 90% passages from the cell population of the seed cell bank are clump passages. 275. The method of any one of embodiments 258 to 274, wherein at least 95% passages from the cell population of the seed cell bank are clump passages. 276. The method of any one of embodiments 258 to 275, wherein 100% passages from the cell population of the seed cell bank are clump passages. 277. The method of any one of embodiments 270 to 276, wherein the clump passages are performed in the presence of EDTA. 278. The method of embodiment 277, wherein the clump passages are performed by incubating a cell culture with 0.4-0.6 mM (e.g., 0.5 mM) EDTA. 279. The method of embodiment 277 or embodiment 278 wherein the clump passages are performed by incubating a cell culture with EDTA at a temperature below 40°C (e.g., below 40°C and optionally at least 15°C, or below 37°C and optionally at least 15°C). 280. The method of any one of embodiment 277 to 279, wherein the clump passages are performed by incubating a cell culture with EDTA at room temperature (e.g., at a temperature of 19°C-23°C). 281. The method of any one of embodiments 277 to 279, wherein the clump passages are performed by incubating a cell culture with EDTA for 5-50 minutes (e.g., for 7-20 minutes or 30-45 minutes). 282. The method of any one of embodiments 277 to 279, wherein the clump passages are performed by incubating a cell culture with EDTA for 5-25 minutes (e.g., for 7-20 minutes).283. The method of embodiment 282, wherein the clump passages are performed by incubating a cell culture with EDTA for no more than 7 minutes (e.g., 7 minutes, 6 minutes, or 5 minutes). 284. The method of embodiment 282, wherein the clump passages are performed by incubating a cell culture with EDTA for 7-20 minutes. 285. The method of embodiment 282, wherein the clump passages are performed by incubating a cell culture with EDTA for 8-11 minutes. 286. The method of embodiment 282, wherein the clump passages are performed by incubating a cell culture with EDTA for 8-15 minutes. 287. The method of embodiment 282, wherein the clump passages are performed by incubating a cell culture with EDTA for 8-20 minutes. 288. The method of any one of embodiments 277 to 279, wherein the clump passages are performed by incubating a cell culture with EDTA for 25-50 minutes (e.g., for 30- 45 minutes). 289. The method of embodiment 288, wherein the clump passages are performed by incubating a cell culture with EDTA for 30-45 minutes. 290. The method of embodiment 288, wherein the clump passages are performed by incubating a cell culture with EDTA for 25-35 minutes. 291. The method of embodiment 288, wherein the clump passages are performed by incubating a cell culture with EDTA for 30-40 minutes. 292. The method of embodiment 288, wherein the clump passages are performed by incubating a cell culture with EDTA for 35-45 minutes. 293. The method of embodiment 288, wherein the clump passages are performed by incubating a cell culture with EDTA for 40-50 minutes. 294. The method of any one of embodiments 270 to 293, wherein the clump passages are performed in the absence of a protease treatment, optionally in the absence of any exogenous enzymatic treatment. 295. The method of any one of embodiments 258 to 294, wherein at least half the passages from the cell population of the seed cell bank are performed with a medium comprising one or more supplements, e.g., one or more cell protection supplements. 296. The method of any one of embodiments 258 to 295, wherein at least 60% of the passages from the cell population of the seed cell bank are performed with a medium comprising one or more supplements, e.g., one or more cell protection supplements. 297. The method of any one of embodiments 258 to 296, wherein at least 70% of the passages from the cell population of the seed cell bank are performed with a medium comprising one or more supplements, e.g., one or more cell protection supplements.298. The method of any one of embodiments 258 to 297, wherein at least 80% of the passages from the cell population of the seed cell bank are performed with a medium comprising one or more supplements, e.g., one or more cell protection supplements. 299. The method of any one of embodiments 258 to 298, wherein at least 90% of the passages from the cell population of the seed cell bank are performed with a medium comprising one or more supplements, e.g., one or more cell protection supplements. 300. The method of any one of embodiments 258 to 299, wherein at least 95% of the passages from the cell population of the seed cell bank are performed with a medium comprising one or more supplements, e.g., one or more cell protection supplements. 301. The method of any one of embodiments 258 to 300, wherein 100% of the passages from the cell population of the seed cell bank are performed with a medium comprising one or more supplements, e.g., one or more cell protection supplements. 302. The method of any one of embodiments 295 to 301, wherein the one or more supplements comprise one or more ROCK inhibitors. 303. The method of embodiment 302, wherein the one or more ROCK inhibitors comprise Y-27632. 304. The method of embodiment 302 or embodiment 303, wherein the one or more ROCK inhibitors comprise chroman 1. 305. The method of any one of embodiments 302 to 304, wherein the one or more supplements comprises a supplement cocktail, e.g., a cell protection supplement cocktail. 306. The method of embodiment 305, wherein the supplement cocktail comprises CEPT (chroman 1, emricasan, polyamines, and trans-ISRIB) cocktail. 307. The method of any one of embodiments 258 to 306, wherein the master cell bank is the progeny of at least two expansions in culture from an ancestral cell population 308. The method of embodiment 307, wherein a majority of phases of a majority of expansions are performed in the presence of at least one laminin moiety. 309. The method of embodiment 307, wherein a majority of phases of all expansions are performed in the presence of at least one laminin moiety. 310. The method of embodiment 307, wherein all phases of a majority of expansions are performed in the presence of at least one laminin moiety. 311. The method of embodiment 307, wherein all phases of all expansions are performed in the presence of at least one laminin moiety. 312. The method of any one of embodiments 308 to 311, wherein the at least one laminin moiety comprises a full-length laminin and / or a laminin fragment. 313. The method of any one of embodiments 308 to 312, wherein the at least one laminin moiety is a trimer comprising a laminin alpha, a laminin beta and a laminin gamma.314. The method of embodiment 313, wherein the laminin alpha comprises an amino acid sequence having at least 77% sequence identity to the amino acid sequence of SEQ ID NO:4. 315. The method of embodiment 313, wherein the laminin alpha comprises an amino acid sequence having at least 77% sequence identity to the amino acid sequence of SEQ ID NO:5. 316. The method of embodiment 313, wherein the laminin alpha comprises an amino acid sequence having at least 77% sequence identity to the amino acid sequence of SEQ ID NO:6. 317. The method of any one of embodiments 313 to 316, wherein the laminin beta comprises an amino acid sequence having at least 93% sequence identity to the amino acid sequence of SEQ ID NO:15 and includes the amino acid sequence of SEQ ID NO:17. 318. The method of any one of embodiments 313 to 316, wherein the laminin beta comprises an amino acid sequence having at least 93% sequence identity to the amino acid sequence of SEQ ID NO:16 and includes the amino acid sequence of SEQ ID NO:18. 319. The method of any one of embodiments 313 to 318, wherein the laminin gamma comprises an amino acid sequence having at least 89% sequence identity to the amino acid sequence of SEQ ID NO:27 and includes the amino acid sequence of SEQ ID NO:29. 320. The method of any one of embodiments 313 to 318, wherein the laminin gamma comprises an amino acid sequence having at least 89% sequence identity to the amino acid sequence of SEQ ID NO:28 and includes the amino acid sequence of SEQ ID NO:30. 321. The method of any one of embodiments 313 to 320, wherein the laminin alpha comprises an amino acid sequence having at least 79% sequence identity to the amino acid sequence of SEQ ID NO:31. 322. The method of any one of embodiments 313 to 320, wherein the laminin alpha comprises an amino acid sequence having at least 79% sequence identity to the amino acid sequence of SEQ ID NO:32. 323. The method of any one of embodiments 313 to 320, wherein the laminin alpha comprises an amino acid sequence having at least 79% sequence identity to the amino acid sequence of SEQ ID NO:33. 324. The method of any one of embodiments 313 to 323, wherein the laminin beta comprises an amino acid sequence having at least 88% sequence identity to the amino acid sequence of SEQ ID NO:36. 325. The method of any one of embodiments 313 to 323, wherein the laminin beta comprises an amino acid sequence having at least 88% sequence identity to the amino acid sequence of SEQ ID NO: 37.326. The method of any one of embodiments 313 to 325, wherein the laminin gamma comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO:38. 327. The method of any one of embodiments 313 to 325, wherein the laminin gamma comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO:39. 328. The method of any one of embodiments 308 to 327, wherein the at least one laminin moiety comprises LN521. 329. The method of any one of embodiments 308 to 328, wherein the laminin moiety comprises LN-511-E8. 330. The method of any one of embodiments 308 to 329, wherein a majority of (optionally all) phases of a majority of (optionally all) expansions are performed in the absence of a vitronectin (e.g., in the absence of VTN-1 and / or VTN-2). 331. The method of any one of embodiments 308 to 330, wherein a majority of (optionally all) phases of a majority of (optionally all) expansions are performed in the absence of a cadherin (e.g., in the absence of e-cadherin). 332. The method of any one of embodiments 308 to 331, wherein a majority of (optionally all) phases of a majority of (optionally all) expansions are performed in the absence of a cell feeder layer. 333. The method of any one of embodiments 308 to 332, wherein a majority of (optionally all) phases of a majority of (optionally all) expansions are performed on an adherent surface. 334. The method of any one of embodiments 308 to 333, wherein a majority of (optionally all) phases of a majority of (optionally all) expansions are performed on a surface treated for increased PSC adherence, optionally wherein the surface is treated for increased hydrophilicity. 335. The method of any one of embodiments 308 to 334, wherein a majority of (optionally all) phases of a majority of (optionally all) expansions are performed on a surface comprising means for increased PSC adherence. 336. The method of any one of embodiments 308 to 335, wherein a majority of (optionally all) phases of a majority of (optionally all) expansions are performed on a tissue culture treated vessel surface, optionally wherein the tissue culture treated vessel surface is (a) a ThermoFisher Nunclon™ Delta-treated surface, (b) an Azer Scientific tissue culture treated surface, (c) an equivalent of (a) and / or (b), or (d) any combination of (a), (b) and (c). 337. The method of any one of embodiments 258 to 336, wherein the master cell bank is the product of at least one round of cryopreservation and reactivation. 338. The method of any one of embodiments 258 to 337, wherein (a) the prevalence of BCOR SNP1 is less than 1% in the population of cells in the master cell bank and / or (b) (i)population of cells in the master cell bank is a male cell population and the BCOR SNP1 VAF is less than 1% or (ii) population of cells in the master cell bank is a female cell population and the BCOR SNP1 VAF is less than 1%. 339. The method of any one of embodiments 258 to 338, wherein (a) the prevalence of BCOR SNP1 is less than 0.5% in the population of cells in the master cell bank and / or (b) (i) population of cells in the master cell bank is a male cell population and the BCOR SNP1 VAF is less than 0.5% or (ii) population of cells in the master cell bank is a female cell population and the BCOR SNP1 VAF is less than 0.5%. 340. The method of any one of embodiments 258 to 339, wherein (a) the prevalence of BCOR SNP1 is less than 0.1% in the population of cells in the master cell bank and / or (b) (i) population of cells in the master cell bank is a male cell population and the BCOR SNP1 VAF is less than 0.1% or (ii) population of cells in the master cell bank is a female cell population and the BCOR SNP1 VAF is less than 0.1%. 341. The method of any one of embodiments 258 to 340, wherein (a) the prevalence of BCOR SNP1 is less than 0.05% in the population of cells in the master cell bank and / or (b) (i) population of cells in the master cell bank is a male cell population and the BCOR SNP1 VAF is less than 0.05% or (ii) population of cells in the master cell bank is a female cell population and the BCOR SNP1 VAF is less than 0.05%. 342. The method of any one of embodiments 258 to 341, wherein (a) the prevalence of BCOR SNP1 is less than 0.01% in the population of cells in the master cell bank and / or (b) (i) population of cells in the master cell bank is a male cell population and the BCOR SNP1 VAF is less than 0.01% or (ii) population of cells in the master cell bank is a female cell population and the BCOR SNP1 VAF is less than 0.01%. 343. The method of any one of embodiments 258 to 342, wherein (a) the prevalence of BCOR SNP2 is less than 1% in the population of cells in the master cell bank and / or (b) (i) population of cells in the master cell bank is a male cell population and the BCOR SNP2 VAF is less than 1% or (ii) population of cells in the master cell bank is a female cell population and the BCOR SNP2 VAF is less than 1%. 344. The method of any one of embodiments 258 to 343, wherein (a) the prevalence of BCOR SNP2 is less than 0.5% in the population of cells in the master cell bank and / or (b) (i) population of cells in the master cell bank is a male cell population and the BCOR SNP2 VAF is less than 0.5% or (ii) population of cells in the master cell bank is a female cell population and the BCOR SNP2 VAF is less than 0.5%. 345. The method of any one of embodiments 258 to 344, wherein (a) the prevalence of BCOR SNP2 is less than 0.1% in the population of cells in the master cell bank and / or (b) (i) population of cells in the master cell bank is a male cell population and the BCOR SNP2 VAF is less than 0.1% or (ii) population of cells in the master cell bank is a female cell population and the BCOR SNP2 VAF is less than 0.1%.346. The method of any one of embodiments 258 to 345, wherein (a) the prevalence of BCOR SNP2 is less than 0.05% in the population of cells in the master cell bank and / or (b) (i) population of cells in the master cell bank is a male cell population and the BCOR SNP2 VAF is less than 0.05% or (ii) population of cells in the master cell bank is a female cell population and the BCOR SNP2 VAF is less than 0.05%. 347. The method of any one of embodiments 258 to 346, wherein (a) the prevalence of BCOR SNP2 is less than 0.01% in the population of cells in the master cell bank and / or (b) (i) population of cells in the master cell bank is a male cell population and the BCOR SNP2 VAF is less than 0.01% or (ii) population of cells in the master cell bank is a female cell population and the BCOR SNP2 VAF is less than 0.01%. 348. The method of any one of embodiments 258 to 347, wherein the prevalence of RARA SNP in cells of the master cell bank is less than 1%. 349. The method of any one of embodiments 258 to 348, wherein the prevalence of RARA SNP in cells of the master cell bank is less than 0.5%. 350. The method of any one of embodiments 258 to 349, wherein the prevalence of RARA SNP in cells of the master cell bank is less than 0.1%. 351. The method of any one of embodiments 258 to 350, wherein the prevalence of RARA SNP in cells of the master cell bank is less than 0.05%. 352. The method of any one of embodiments 258 to 351, wherein the prevalence of RARA SNP in cells of the master cell bank is less than 0.01%. 353. The method of any one of embodiments 258 to 352, wherein the seed cell bank is a seed cell bank produced by the method of any one of embodiments 167 to 257. 354. The method of any one of embodiments 258 to 353, wherein the population of cells of the seed cell bank is a population of iPSCs. 355. A method of producing a working cell bank comprising a genomically stabilized population of PSCs, comprising: (a) expanding one or more cells of a master cell bank in culture in the presence of a laminin moiety under conditions in which a genomically stabilized population of PSCs is produced; (b) dispensing genomically stabilized population of PSCs produced in step (a) into cryopreservation containers; and (c) subjecting the cryopreservation containers to cryopreservation conditions, thereby producing a working cell bank. 356. A method of producing a working cell bank comprising a genomically stabilized population of PSCs, comprising: (a) expanding one or more cells of a master cell bank in culture in the presence of a one or more supplements, e.g., one or more cell protectionsupplements under conditions in which a genomically stabilized population of PSCs is produced; (b) dispensing genomically stabilized population of PSCs produced in step (a) into cryopreservation containers; and (c) subjecting the cryopreservation containers to cryopreservation conditions, thereby producing a working cell bank 357. The method of embodiment 356, wherein the one or more supplements comprise one or more ROCK inhibitors. 358. The method of embodiment 357, wherein the one or more ROCK inhibitors comprise Y-27632. 359. The method embodiment 357 or embodiment 358, wherein the one or more ROCK inhibitors comprise chroman 1. 360. The method of any one of embodiments 356 to 359, wherein the one or more supplements comprises a supplement cocktail, e.g., a cell protection supplement cocktail. 361. The method of embodiment 360, wherein the supplement cocktail comprises CEPT (chroman 1, emricasan, polyamines, and trans-ISRIB) cocktail. 362. The method of any one of embodiments 356 to 361, wherein step (a) is performed in the presence of a laminin moiety. 363. The method of any one of embodiments 355 to 362, wherein step (a) comprises at least 3 (e.g., 3) passages of the cell population of the master cell bank and its progeny. 364. The method of any one of embodiments 355 to 362, wherein step (a) comprises at least 4 (e.g., 4) passages of the cell population of the master cell bank and its progeny. 365. The method of any one of embodiments 355 to 362, wherein step (a) comprises at least 5 (e.g., 5) passages of the cell population of the master cell bank and its progeny. 366. The method of any one of embodiments 355 to 365, wherein step (a) comprises up to 6 or up to 7 passages of the cell population of the master cell bank and its progeny. 367. The method of any one of embodiments 355 to 366, wherein at least half the passages from the cell population of the master cell bank are clump passages. 368. The method of any one of embodiments 355 to 367, wherein at least 60% passages from the cell population of the master cell bank are clump passages. 369. The method of any one of embodiments 355 to 368, wherein at least 70% passages from the cell population of the master cell bank are clump passages. 370. The method of any one of embodiments 355 to 369, wherein at least 80% passages from the cell population of the master cell bank are clump passages. 371. The method of any one of embodiments 355 to 370, wherein at least 90% passages from the cell population of the master cell bank are clump passages.372. The method of any one of embodiments 355 to 371, wherein 100% passages from the cell population of the master cell bank are clump passages. 373. The method of any one of embodiments 367 to 372, wherein the clump passages are performed in the presence of EDTA. 374. The method of embodiment 373, wherein the clump passages are performed by incubating a cell culture with 0.4-0.6 mM (e.g., 0.5 mM) EDTA. 375. The method of embodiment 373 or embodiment 374, wherein the clump passages are performed by incubating a cell culture with EDTA at a temperature below 40°C (e.g., below 40°C and optionally at least 15°C, or below 37°C and optionally at least 15°C). 376. The method of any one of embodiments 373 to 375, wherein the clump passages are performed by incubating a cell culture with EDTA at room temperature (e.g., at a temperature of 19°C-23°C). 377. The method of any one of embodiments 373 to 376, wherein the clump passages are performed by incubating a cell culture with EDTA for 5-50 minutes (e.g., for 7-20 minutes or 30-45 minutes). 378. The method of any one of embodiments 373 to 376, wherein the clump passages are performed by incubating a cell culture with EDTA for 5-25 minutes (e.g., for 7-20 minutes). 379. The method of embodiment 378, wherein the clump passages are performed by incubating a cell culture with EDTA for no more than 7 minutes (e.g., 7 minutes, 6 minutes, or 5 minutes). 380. The method of embodiment 378, wherein the clump passages are performed by incubating a cell culture with EDTA for 7-20 minutes. 381. The method of embodiment 378, wherein the clump passages are performed by incubating a cell culture with EDTA for 8-11 minutes. 382. The method of embodiment 378, wherein the clump passages are performed by incubating a cell culture with EDTA for 8-15 minutes. 383. The method of embodiment 378, wherein the clump passages are performed by incubating a cell culture with EDTA for 8-20 minutes. 384. The method of any one of embodiments 373 to 376, wherein the clump passages are performed by incubating a cell culture with EDTA for 25-50 minutes (e.g., for 30- 45 minutes). 385. The method of embodiment 384, wherein the clump passages are performed by incubating a cell culture with EDTA for 30-45 minutes. 386. The method of embodiment 384, wherein the clump passages are performed by incubating a cell culture with EDTA for 25-35 minutes. 387. The method of embodiment 384, wherein the clump passages are performed by incubating a cell culture with EDTA for 30-40 minutes.388. The method of embodiment 384, wherein the clump passages are performed by incubating a cell culture with EDTA for 35-45 minutes. 389. The method of embodiment 384, wherein the clump passages are performed by incubating a cell culture with EDTA for 40-50 minutes. 390. The method of any one of embodiments 367 to 389, wherein the clump passages are performed in the absence of a protease treatment, optionally in the absence of any exogenous enzymatic treatment. 391. The method of any one of embodiments 355 to 390, wherein at least half the passages from the cell population of the master cell bank are performed with a medium comprising one or more supplements, e.g., one or more cell protection supplements. 392. The method of any one of embodiments 355 to 391, wherein at least 60% of the passages from the cell population of the master cell bank are performed with a medium comprising one or more supplements, e.g., one or more cell protection supplements. 393. The method of any one of embodiments 355 to 392, wherein at least 70% of the passages from the cell population of the master cell bank are performed with a medium comprising one or more supplements, e.g., one or more cell protection supplements. 394. The method of any one of embodiments 355 to 393, wherein at least 80% of the passages from the cell population of the master cell bank are performed with a medium comprising one or more supplements, e.g., one or more cell protection supplements. 395. The method of any one of embodiments 355 to 394, wherein at least 90% of the passages from the cell population of the master cell bank are performed with a medium comprising one or more supplements, e.g., one or more cell protection supplements. 396. The method of any one of embodiments 355 to 395, wherein 100% of the passages from the cell population of the master cell bank are performed with a medium comprising one or more supplements, e.g., one or more cell protection supplements. 397. The method of any one of embodiments 391 to 396, wherein the one or more supplements comprise one or more ROCK inhibitors. 398. The method of embodiment 397, wherein the one or more ROCK inhibitors comprise Y-27632. 399. The method of embodiment 397 or embodiment 398, wherein the one or more ROCK inhibitors comprise chroman 1. 400. The method of any one of embodiments 391 to 399, wherein the one or more supplements comprises a supplement cocktail, e.g., a cell protection supplement cocktail. 401. The method of embodiment 400, wherein the supplement cocktail comprises CEPT (chroman 1, emricasan, polyamines, and trans-ISRIB) cocktail. 402. The method of any one of embodiments 355 to 401, wherein the working cell bank is the progeny of at least 3 expansions in culture from an ancestral cell population.403. The method of embodiment 402, wherein a majority of phases of a majority of expansions are performed in the presence of at least one laminin moiety. 404. The method of embodiment 402, wherein a majority of phases of all expansions are performed in the presence of at least one laminin moiety. 405. The method of embodiment 402, wherein all phases of a majority of expansions are performed in the presence of at least one laminin moiety. 406. The method of embodiment 402, wherein all phases of all expansions are performed in the presence of at least one laminin moiety. 407. The method of any one of embodiments 403 to 406, wherein the at least one laminin moiety comprises a full-length laminin and / or a laminin fragment. 408. The method of any one of embodiments 403 to 407, wherein the at least one laminin moiety is a trimer comprising a laminin alpha, a laminin beta and a laminin gamma. 409. The method of embodiment 408, wherein the laminin alpha comprises an amino acid sequence having at least 77% sequence identity to the amino acid sequence of SEQ ID NO:4. 410. The method of embodiment 408, wherein the laminin alpha comprises an amino acid sequence having at least 77% sequence identity to the amino acid sequence of SEQ ID NO:5. 411. The method of embodiment 408, wherein the laminin alpha comprises an amino acid sequence having at least 77% sequence identity to the amino acid sequence of SEQ ID NO:6. 412. The method of any one of embodiments 408 to 411, wherein the laminin beta comprises an amino acid sequence having at least 93% sequence identity to the amino acid sequence of SEQ ID NO:15 and includes the amino acid sequence of SEQ ID NO:17. 413. The method of any one of embodiments 408 to 411, wherein the laminin beta comprises an amino acid sequence having at least 93% sequence identity to the amino acid sequence of SEQ ID NO:16 and includes the amino acid sequence of SEQ ID NO:18. 414. The method of any one of embodiments 408 to 413, wherein the laminin gamma comprises an amino acid sequence having at least 89% sequence identity to the amino acid sequence of SEQ ID NO:27 and includes the amino acid sequence of SEQ ID NO:29. 415. The method of any one of embodiments 408 to 413, wherein the laminin gamma comprises an amino acid sequence having at least 89% sequence identity to the amino acid sequence of SEQ ID NO:28 and includes the amino acid sequence of SEQ ID NO:30. 416. The method of any one of embodiments 408 to 415, wherein the laminin alpha comprises an amino acid sequence having at least 79% sequence identity to the amino acid sequence of SEQ ID NO:31.417. The method of any one of embodiments 408 to 415, wherein the laminin alpha comprises an amino acid sequence having at least 79% sequence identity to the amino acid sequence of SEQ ID NO:32. 418. The method of any one of embodiments 408 to 415, wherein the laminin alpha comprises an amino acid sequence having at least 79% sequence identity to the amino acid sequence of SEQ ID NO:33. 419. The method of any one of embodiments 408 to 418, wherein the laminin beta comprises an amino acid sequence having at least 88% sequence identity to the amino acid sequence of SEQ ID NO:36. 420. The method of any one of embodiments 408 to 418, wherein the laminin beta comprises an amino acid sequence having at least 88% sequence identity to the amino acid sequence of SEQ ID NO: 37. 421. The method of any one of embodiments 408 to 420, wherein the laminin gamma comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO:38. 422. The method of any one of embodiments 408 to 420, wherein the laminin gamma comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO:39. 423. The method of any one of embodiments 408 to 422, wherein the at least one laminin moiety comprises LN521. 424. The method of embodiment any one of embodiments 408 to 423, wherein the laminin moiety comprises LN-511-E8. 425. The method of any one of embodiments 402 to 424, wherein a majority of (optionally all) phases of a majority of (optionally all) expansions are performed in the absence of a vitronectin (e.g., in the absence of VTN-1 and / or VTN-2). 426. The method of any one of embodiments 402 to 425, wherein a majority of (optionally all) phases of a majority of (optionally all) expansions are performed in the absence of a cadherin (e.g., in the absence of e-cadherin). 427. The method of any one of embodiments 402 to 426, wherein a majority of (optionally all) phases of a majority of (optionally all) expansions are performed in the absence of a cell feeder layer. 428. The method of any one of embodiments 402 to 427, wherein a majority of (optionally all) phases of a majority of (optionally all) expansions are performed on an adherent surface. 429. The method of any one of embodiments 402 to 428, wherein a majority of (optionally all) phases of a majority of (optionally all) expansions are performed on a surface treated for increased PSC adherence, optionally wherein the surface is treated for increased hydrophilicity.430. The method of any one of embodiments 402 to 429, wherein a majority of (optionally all) phases of a majority of (optionally all) expansions are performed on a surface comprising means for increased PSC adherence. 431. The method of any one of embodiments 402 to 430, wherein a majority of (optionally all) phases of a majority of (optionally all) expansions are performed on a tissue culture treated vessel surface, optionally wherein the tissue culture treated vessel surface is (a) a ThermoFisher Nunclon™ Delta-treated surface, (b) an Azer Scientific tissue culture treated surface, (c) an equivalent of (a) and / or (b), or (d) any combination of (a), (b) and (c). 432. The method of any one of embodiments 355 to 431, wherein the working cell bank is the product of at least two rounds of cryopreservation and reactivation. 433. The method of any one of embodiments 355 to 432, wherein (a) the prevalence of BCOR SNP1 is less than 1% in the population of cells in the working cell bank and / or (b) (i) population of cells in the working cell bank is a male cell population and the BCOR SNP1 VAF is less than 1% or (ii) population of cells in the working cell bank is a female cell population and the BCOR SNP1 VAF is less than 1%. 434. The method of any one of embodiments 355 to 433, wherein (a) the prevalence of BCOR SNP1 is less than 0.5% in the population of cells in the working cell bank and / or (b) (i) population of cells in the working cell bank is a male cell population and the BCOR SNP1 VAF is less than 0.5% or (ii) population of cells in the working cell bank is a female cell population and the BCOR SNP1 VAF is less than 0.5%. 435. The method of any one of embodiments 355 to 434, wherein (a) the prevalence of BCOR SNP1 is less than 0.1% in the population of cells in the working cell bank and / or (b) (i) population of cells in the working cell bank is a male cell population and the BCOR SNP1 VAF is less than 0.1% or (ii) population of cells in the working cell bank is a female cell population and the BCOR SNP1 VAF is less than 0.1%. 436. The method of any one of embodiments 355 to 435, wherein (a) the prevalence of BCOR SNP1 is less than 0.05% in the population of cells in the working cell bank and / or (b) (i) population of cells in the working cell bank is a male cell population and the BCOR SNP1 VAF is less than 0.05% or (ii) population of cells in the working cell bank is a female cell population and the BCOR SNP1 VAF is less than 0.05%. 437. The method of any one of embodiments 355 to 436, wherein (a) the prevalence of BCOR SNP1 is less than 0.01% in the population of cells in the working cell bank and / or (b) (i) population of cells in the working cell bank is a male cell population and the BCOR SNP1 VAF is less than 0.01% or (ii) population of cells in the working cell bank is a female cell population and the BCOR SNP1 VAF is less than 0.01%. 438. The method of any one of embodiments 355 to 437, wherein (a) the prevalence of BCOR SNP2 is less than 1% in the population of cells in the working cell bank and / or (b) (i) population of cells in the working cell bank is a male cell population and the BCOR SNP2 VAFis less than 1% or (ii) population of cells in the working cell bank is a female cell population and the BCOR SNP2 VAF is less than 1%. 439. The method of any one of embodiments 355 to 438, wherein (a) the prevalence of BCOR SNP2 is less than 0.5% in the population of cells in the working cell bank and / or (b) (i) population of cells in the working cell bank is a male cell population and the BCOR SNP2 VAF is less than 0.5% or (ii) population of cells in the working cell bank is a female cell population and the BCOR SNP2 VAF is less than 0.5%. 440. The method of any one of embodiments 355 to 439, wherein (a) the prevalence of BCOR SNP2 is less than 0.1% in the population of cells in the working cell bank and / or (b) (i) population of cells in the working cell bank is a male cell population and the BCOR SNP2 VAF is less than 0.1% or (ii) population of cells in the working cell bank is a female cell population and the BCOR SNP2 VAF is less than 0.1%. 441. The method of any one of embodiments 355 to 440, wherein (a) the prevalence of BCOR SNP2 is less than 0.05% in the population of cells in the working cell bank and / or (b) (i) population of cells in the working cell bank is a male cell population and the BCOR SNP2 VAF is less than 0.05% or (ii) population of cells in the working cell bank is a female cell population and the BCOR SNP2 VAF is less than 0.05%. 442. The method of any one of embodiments 355 to 441, wherein (a) the prevalence of BCOR SNP2 is less than 0.01% in the population of cells in the working cell bank and / or (b) (i) population of cells in the working cell bank is a male cell population and the BCOR SNP2 VAF is less than 0.01% or (ii) population of cells in the working cell bank is a female cell population and the BCOR SNP2 VAF is less than 0.01%. 443. The method of any one of embodiments 355 to 442, wherein the prevalence of RARA SNP in cells of the working cell bank is less than 1%. 444. The method of any one of embodiments 355 to 443, wherein the prevalence of RARA SNP in cells of the working cell bank is less than 0.5%. 445. The method of any one of embodiments 355 to 444, wherein the prevalence of RARA SNP in cells of the working cell bank is less than 0.1%. 446. The method of any one of embodiments 355 to 445, wherein the prevalence of RARA SNP in cells of the working cell bank is less than 0.05%. 447. The method of any one of embodiments 355 to 446, wherein the prevalence of RARA SNP in cells of the working cell bank is less than 0.01%. 448. The method of any one of embodiments 355 to 447, wherein the master cell bank is a master cell bank produced by the method of any one of embodiments 258 to 354. 449. The method of any one of embodiments 355 to 448, wherein the population of cells of the master cell bank is a population of iPSCs. 450. A method of producing an expanded pluripotent intermediate cell bank comprising a genomically stabilized population of PSCs, comprising:(a) expanding one or more cells of a working cell bank in culture in the presence of a laminin moiety under conditions in which a genomically stabilized population of PSCs is produced; (b) dispensing genomically stabilized population of PSCs produced in step (a) into cryopreservation containers; and (c) subjecting the cryopreservation containers to cryopreservation conditions, thereby producing an intermediate cell bank. 451. A method of producing an expanded pluripotent intermediate cell bank comprising a genomically stabilized population of PSCs, comprising: (a) expanding one or more cells of a working cell bank in culture in the presence of one or more supplements, e.g., cell protection supplements, under conditions in which a genomically stabilized population of PSCs is produced; (b) dispensing genomically stabilized population of PSCs produced in step (a) into cryopreservation containers; and (c) subjecting the cryopreservation containers to cryopreservation conditions, thereby producing an intermediate cell bank. 452. The method of embodiment 451, wherein the one or more supplements comprise one or more ROCK inhibitors. 453. The method of embodiment 451 or embodiment 452, wherein the one or more ROCK inhibitors comprise Y-27632. 454. The method of any one of embodiments 451 to 453, wherein the one or more ROCK inhibitors comprise chroman 1. 455. The method of any one of embodiments 451 to 454, wherein the one or more supplements comprises a supplement cocktail, e.g., a cell protection supplement cocktail. 456. The method of embodiment 455, wherein the supplement cocktail comprises CEPT (chroman 1, emricasan, polyamines, and trans-ISRIB) cocktail. 457. The method of any one of embodiments 451 to 456, wherein step (a) is performed in the presence of a laminin moiety. 458. The method of any one of embodiments 450 to 457, wherein step (a) comprises at least 3 (e.g., 3) passages of the cell population of the working cell bank and its progeny. 459. The method of any one of embodiments 450 to 458, wherein step (a) comprises at least 4 (e.g., 4) passages of the cell population of the working cell bank and its progeny. 460. The method of any one of embodiments 450 to 459, wherein step (a) comprises at least 5 (e.g., 5) passages of the cell population of the working cell bank and its progeny.461. The method of any one of embodiments 450 to 460, wherein step (a) comprises up to 6 or up to 7 passages of the cell population of the working cell bank and its progeny. 462. The method of any one of embodiments 450 to 461, wherein at least half the passages from the cell population of the working cell bank are clump passages. 463. The method of any one of embodiments 450 to 462, wherein at least 60% passages from the cell population of the working cell bank are clump passages. 464. The method of any one of embodiments 450 to 463, wherein at least 70% passages from the cell population of the working cell bank are clump passages. 465. The method of any one of embodiments 450 to 464, wherein at least 80% passages from the cell population of the working cell bank are clump passages. 466. The method of any one of embodiments 450 to 465, wherein at least 90% passages from the cell population of the working cell bank are clump passages. 467. The method of any one of embodiments 450 to 466, wherein 100% passages from the cell population of the working cell bank are clump passages. 468. The method of any one of embodiments 450 to 467, wherein the clump passages are performed in the presence of EDTA. 469. The method of embodiment 468, wherein the clump passages are performed by incubating a cell culture with 0.4-0.6 mM (e.g., 0.5 mM) EDTA. 470. The method of embodiment 468 or embodiment 469, wherein the clump passages are performed by incubating a cell culture with EDTA at a temperature below 40°C (e.g., below 40°C and optionally at least 15°C, or below 37°C and optionally at least 15°C). 471. The method of any one of embodiments 468 to 470, wherein the clump passages are performed by incubating a cell culture with EDTA at room temperature (e.g., at a temperature of 19°C-23°C). 472. The method of any one of embodiments 468 to 471, wherein the clump passages are performed by incubating a cell culture with EDTA for 5-50 minutes (e.g., for 7-20 minutes or 30-45 minutes). 473. The method of any one of embodiments 468 to 471, wherein the clump passages are performed by incubating a cell culture with EDTA for 5-25 minutes (e.g., for 7-20 minutes). 474. The method of embodiment 473, wherein the clump passages are performed by incubating a cell culture with EDTA for no more than 7 minutes (e.g., 7 minutes, 6 minutes, or 5 minutes). 475. The method of embodiment 473, wherein the clump passages are performed by incubating a cell culture with EDTA for 7-20 minutes. 476. The method of embodiment 473, wherein the clump passages are performed by incubating a cell culture with EDTA for 8-11 minutes.477. The method of embodiment 473, wherein the clump passages are performed by incubating a cell culture with EDTA for 8-15 minutes. 478. The method of embodiment 473, wherein the clump passages are performed by incubating a cell culture with EDTA for 8-20 minutes. 479. The method of any one of embodiments 468 to 471, wherein the clump passages are performed by incubating a cell culture with EDTA for 25-50 minutes (e.g., for 30- 45 minutes). 480. The method of embodiment 479, wherein the clump passages are performed by incubating a cell culture with EDTA for 30-45 minutes. 481. The method of embodiment 479, wherein the clump passages are performed by incubating a cell culture with EDTA for 25-35 minutes. 482. The method of embodiment 479, wherein the clump passages are performed by incubating a cell culture with EDTA for 30-40 minutes. 483. The method of embodiment 479, wherein the clump passages are performed by incubating a cell culture with EDTA for 35-45 minutes. 484. The method of embodiment 479, wherein the clump passages are performed by incubating a cell culture with EDTA for 40-50 minutes. 485. The method of any one of embodiments 450 to 484, wherein the clump passages are performed in the absence of a protease treatment, optionally in the absence of any exogenous enzymatic treatment. 486. The method of any one of embodiments 450 to 485, wherein at least half the passages from the cell population of the working cell bank are performed with a medium comprising one or more supplements, e.g., one or more cell protection supplements. 487. The method of any one of embodiments 450 to 486, wherein at least 60% of the passages from the cell population of the working cell bank are performed with a medium comprising one or more supplements, e.g., one or more cell protection supplements. 488. The method of any one of embodiments 450 to 487, wherein at least 70% of the passages from the cell population of the working cell bank are performed with a medium comprising one or more supplements, e.g., one or more cell protection supplements. 489. The method of any one of embodiments 450 to 488, wherein at least 80% of the passages from the cell population of the working cell bank are performed with a medium comprising one or more supplements, e.g., one or more cell protection supplements. 490. The method of any one of embodiments 450 to 489, wherein at least 90% of the passages from the cell population of the working cell bank are performed with a medium comprising one or more supplements, e.g., one or more cell protection supplements. 491. The method of any one of embodiments 450 to 490, wherein 100% of the passages from the cell population of the working cell bank are performed with a medium comprising one or more supplements, e.g., one or more cell protection supplements.492. The method of any one of embodiments 486 to 491, wherein the one or more supplements comprise one or more ROCK inhibitors. 493. The method of embodiment 492, wherein the one or more ROCK inhibitors comprise Y-27632. 494. The method of embodiment 492 or embodiment 493, wherein the one or more ROCK inhibitors comprise chroman 1. 495. The method of any one of embodiments 486 to 494, wherein the one or more supplements comprises a supplement cocktail, e.g., a cell protection supplement cocktail. 496. The method of embodiment 495, wherein the supplement cocktail comprises CEPT (chroman 1, emricasan, polyamines, and trans-ISRIB) cocktail. 497. The method of any one of embodiments 450 to 496, wherein the pluripotent intermediate cell bank is the progeny of at least four expansions in culture from the ancestral cell population. 498. The method of embodiment 497, wherein a majority of phases of a majority of expansions are performed in the presence of at least one laminin moiety. 499. The method of embodiment 497, wherein a majority of phases of all expansions are performed in the presence of at least one laminin moiety. 500. The method of embodiment 497, wherein all phases of a majority of expansions are performed in the presence of at least one laminin moiety. 501. The method of embodiment 497, wherein all phases of all expansions are performed in the presence of at least one laminin moiety. 502. The method of any one of embodiments 498 to 501, wherein the at least one laminin moiety comprises a full-length laminin and / or a laminin fragment. 503. The method of any one of embodiments 498 to 502, wherein the at least one laminin moiety is a trimer comprising a laminin alpha, a laminin beta and a laminin gamma. 504. The method of embodiment 503, wherein the laminin alpha comprises an amino acid sequence having at least 77% sequence identity to the amino acid sequence of SEQ ID NO:4. 505. The method of embodiment 503, wherein the laminin alpha comprises an amino acid sequence having at least 77% sequence identity to the amino acid sequence of SEQ ID NO:5. 506. The method of embodiment 503, wherein the laminin alpha comprises an amino acid sequence having at least 77% sequence identity to the amino acid sequence of SEQ ID NO:6. 507. The method of any one of embodiments 503 to 506, wherein the laminin beta comprises an amino acid sequence having at least 93% sequence identity to the amino acid sequence of SEQ ID NO:15 and includes the amino acid sequence of SEQ ID NO:17.508. The method of any one of embodiments 503 to 506, wherein the laminin beta comprises an amino acid sequence having at least 93% sequence identity to the amino acid sequence of SEQ ID NO:16 and includes the amino acid sequence of SEQ ID NO:18. 509. The method of any one of embodiments 503 to 508, wherein the laminin gamma comprises an amino acid sequence having at least 89% sequence identity to the amino acid sequence of SEQ ID NO:27 and includes the amino acid sequence of SEQ ID NO:29. 510. The method of any one of embodiments 503 to 508, wherein the laminin gamma comprises an amino acid sequence having at least 89% sequence identity to the amino acid sequence of SEQ ID NO:28 and includes the amino acid sequence of SEQ ID NO:30. 511. The method of any one of embodiments 503 to 510, wherein the laminin alpha comprises an amino acid sequence having at least 79% sequence identity to the amino acid sequence of SEQ ID NO:31. 512. The method of any one of embodiments 503 to 510, wherein the laminin alpha comprises an amino acid sequence having at least 79% sequence identity to the amino acid sequence of SEQ ID NO:32. 513. The method of any one of embodiments 503 to 510, wherein the laminin alpha comprises an amino acid sequence having at least 79% sequence identity to the amino acid sequence of SEQ ID NO:33. 514. The method of any one of embodiments 503 to 513, wherein the laminin beta comprises an amino acid sequence having at least 88% sequence identity to the amino acid sequence of SEQ ID NO:36. 515. The method of any one of embodiments 503 to 513, wherein the laminin beta comprises an amino acid sequence having at least 88% sequence identity to the amino acid sequence of SEQ ID NO: 37. 516. The method of any one of embodiments 503 to 515, wherein the laminin gamma comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO:38. 517. The method of any one of embodiments 503 to 515, wherein the laminin gamma comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO:39. 518. The method of any one of embodiments 503 to 517, wherein the at least one laminin moiety comprises LN521. 519. The method of any one of embodiments 503 to 518, wherein the laminin moiety comprises LN-511-E8. 520. The method of any one of embodiments 497 to 519, wherein a majority of (optionally all) phases of a majority of (optionally all) expansions are performed in the absence of a vitronectin (e.g., in the absence of VTN-1 and / or VTN-2).521. The method of any one of embodiments 497 to 520, wherein a majority of (optionally all) phases of a majority of (optionally all) expansions are performed in the absence of a cadherin (e.g., in the absence of e-cadherin). 522. The method of any one of embodiments 497 to 521, wherein a majority of (optionally all) phases of a majority of (optionally all) expansions are performed in the absence of a cell feeder layer. 523. The method of any one of embodiments 497 to 522, wherein a majority of (optionally all) phases of a majority of (optionally all) expansions are performed on an adherent surface. 524. The method of any one of embodiments 497 to 523, wherein a majority of (optionally all) phases of a majority of (optionally all) expansions are performed on a surface treated for increased PSC adherence, optionally wherein the surface is treated for increased hydrophilicity. 525. The method of any one of embodiments 497 to 524, wherein a majority of (optionally all) phases of a majority of (optionally all) expansions are performed on a surface comprising means for increased PSC adherence. 526. The method of any one of embodiments 497 to 525, wherein a majority of (optionally all) phases of a majority of (optionally all) expansions are performed on a tissue culture treated vessel surface, optionally wherein the tissue culture treated vessel surface is (a) a ThermoFisher Nunclon™ Delta-treated surface, (b) an Azer Scientific tissue culture treated surface, (c) an equivalent of (a) and / or (b), or (d) any combination of (a), (b) and (c). 527. The method of any one of embodiments 450 to 526, wherein the pluripotent intermediate cell bank is the product of at least two rounds of cryopreservation and reactivation. 528. The method of any one of embodiments 450 to 527, wherein (a) the prevalence of BCOR SNP1 is less than 1% in the population of cells in the pluripotent intermediate cell bank and / or (b) (i) population of cells in the pluripotent intermediate cell bank is a male cell population and the BCOR SNP1 VAF is less than 1% or (ii) population of cells in the pluripotent intermediate cell bank is a female cell population and the BCOR SNP1 VAF is less than 1%. 529. The method of any one of embodiments 450 to 528, wherein (a) the prevalence of BCOR SNP1 is less than 0.5% in the population of cells in the pluripotent intermediate cell bank and / or (b) (i) population of cells in the pluripotent intermediate cell bank is a male cell population and the BCOR SNP1 VAF is less than 0.5% or (ii) population of cells in the pluripotent intermediate cell bank is a female cell population and the BCOR SNP1 VAF is less than 0.5%. 530. The method of any one of embodiments 450 to 529, wherein (a) the prevalence of BCOR SNP1 is less than 0.1% in the population of cells in the pluripotent intermediate cell bank and / or (b) (i) population of cells in the pluripotent intermediate cell bank is a male cell population and the BCOR SNP1 VAF is less than 0.1% or (ii) population of cells in thepluripotent intermediate cell bank is a female cell population and the BCOR SNP1 VAF is less than 0.1%. 531. The method of any one of embodiments 450 to 530, wherein (a) the prevalence of BCOR SNP1 is less than 0.05% in the population of cells in the pluripotent intermediate cell bank and / or (b) (i) population of cells in the pluripotent intermediate cell bank is a male cell population and the BCOR SNP1 VAF is less than 0.05% or (ii) population of cells in the pluripotent intermediate cell bank is a female cell population and the BCOR SNP1 VAF is less than 0.05%. 532. The method of any one of embodiments 450 to 531, wherein (a) the prevalence of BCOR SNP1 is less than 0.01% in the population of cells in the pluripotent intermediate cell bank and / or (b) (i) population of cells in the pluripotent intermediate cell bank is a male cell population and the BCOR SNP1 VAF is less than 0.01% or (ii) population of cells in the pluripotent intermediate cell bank is a female cell population and the BCOR SNP1 VAF is less than 0.01%. 533. The method of any one of embodiments 450 to 532, wherein (a) the prevalence of BCOR SNP2 is less than 1% in the population of cells in the pluripotent intermediate cell bank and / or (b) (i) population of cells in the pluripotent intermediate cell bank is a male cell population and the BCOR SNP2 VAF is less than 1% or (ii) population of cells in the pluripotent intermediate cell bank is a female cell population and the BCOR SNP2 VAF is less than 1%. 534. The method of any one of embodiments 450 to 533, wherein (a) the prevalence of BCOR SNP2 is less than 0.5% in the population of cells in the pluripotent intermediate cell bank and / or (b) (i) population of cells in the pluripotent intermediate cell bank is a male cell population and the BCOR SNP2 VAF is less than 0.5% or (ii) population of cells in the pluripotent intermediate cell bank is a female cell population and the BCOR SNP2 VAF is less than 0.5%. 535. The method of any one of embodiments 450 to 534, wherein (a) the prevalence of BCOR SNP2 is less than 0.1% in the population of cells in the pluripotent intermediate cell bank and / or (b) (i) population of cells in the pluripotent intermediate cell bank is a male cell population and the BCOR SNP2 VAF is less than 0.1% or (ii) population of cells in the pluripotent intermediate cell bank is a female cell population and the BCOR SNP2 VAF is less than 0.1%. 536. The method of any one of embodiments 450 to 535, wherein (a) the prevalence of BCOR SNP2 is less than 0.05% in the population of cells in the pluripotent intermediate cell bank and / or (b) (i) population of cells in the pluripotent intermediate cell bank is a male cell population and the BCOR SNP2 VAF is less than 0.05% or (ii) population of cells in the pluripotent intermediate cell bank is a female cell population and the BCOR SNP2 VAF is less than 0.05%.537. The method of any one of embodiments 450 to 536, wherein (a) the prevalence of BCOR SNP2 is less than 0.01% in the population of cells in the pluripotent intermediate cell bank and / or (b) (i) population of cells in the pluripotent intermediate cell bank is a male cell population and the BCOR SNP2 VAF is less than 0.01% or (ii) population of cells in the pluripotent intermediate cell bank is a female cell population and the BCOR SNP2 VAF is less than 0.01%. 538. The method of any one of embodiments 450 to 537, wherein the prevalence of RARA SNP in cells of the pluripotent intermediate cell bank is less than 1%. 539. The method of any one of embodiments 450 to 538, wherein the prevalence of RARA SNP in cells of the pluripotent intermediate cell bank is less than 0.5%. 540. The method of any one of embodiments 450 to 539, wherein the prevalence of RARA SNP in cells of the pluripotent intermediate cell bank is less than 0.1%. 541. The method of any one of embodiments 450 to 540, wherein the prevalence of RARA SNP in cells of the pluripotent intermediate cell bank is less than 0.05%. 542. The method of any one of embodiments 450 to 541, wherein the prevalence of RARA SNP in cells of the pluripotent intermediate cell bank is less than 0.01%. 543. The method of any one of embodiments 450 to 542, wherein the working cell bank is a working cell bank produced by the method of any one of embodiments 355 to 449. 544. The method of any one of embodiments 450 to 543, wherein the population of cells of the working cell bank is a population of iPSCs. 545. The method of any one of embodiments 167 to 544, wherein the expanding of step (a) is performed in a culture medium comprising heat-stabilized fibroblast growth factor 2 (FGF2), basic fibroblast growth factor (e.g., rh bFGF), transforming growth factor beta (e.g., rh TGFβ), or a combination thereof. 546. The method of embodiment 545, wherein the medium comprises FGF2. 547. The method of embodiment 545 or 546, wherein the medium comprises bFGF (e.g., rh bFGF). 548. The method of any one of embodiments 545 to 547, wherein the medium comprises TGFβ (e.g., rh TGFβ). 549. The method of any one of embodiments 545 to 548, wherein the medium comprises CTS-E8, eTeSR™, mTeSR™ Plus, mTeSR™ 1, StemFit®, xCellerate™, or iPS Brew XF™ medium. 550. The method of embodiment 549, wherein the medium comprises CTS-E8 medium. 551. The method of embodiment 549, wherein the medium comprises eTeSR™ medium. 552. The method of embodiment 549, wherein the medium comprises mTeSR™ Plus medium.553. The method of embodiment 549, wherein the medium comprises mTeSR™ 1 medium. 554. The method of embodiment 549, wherein the medium comprises StemFit® medium. 555. The method of embodiment 549, wherein the medium comprises xCellerate™ medium. 556. The method of embodiment 549, wherein the medium comprises iPS Brew XF™ medium. 557. A method of producing a genomically stabilized population of PSCs, e.g., a genomically stabilized population of PSCs according to any of any one of embodiments 1 to 166, comprising reactivating a population of cryopreserved genomically stabilized cells in a seed bank. 558. The method of embodiment 545, further comprising preparing the seed bank by the method of any one of embodiments 167 to 257. 559. A method of producing a genomically stabilized population of PSCs, e.g., a genomically stabilized population of PSCs according to any of any one of embodiments 1 to 166, comprising reactivating a population of cryopreserved genomically stabilized cells in a master cell bank. 560. The method of embodiment 559, further comprising preparing the master cell bank by the method of any one of embodiments 258 to 354. 561. The method of embodiment 559 or 560, wherein the master cell bank is prepared from a seed bank. 562. The method of embodiment 561, further comprising preparing the seed bank by the method of any one of embodiments 167 to 257. 563. A method of producing a genomically stabilized population of PSCs in culture, e.g., a genomically stabilized population of PSCs according to any of any one of embodiments 1 to 166, comprising reactivating a population of cryopreserved genomically stabilized cells in a working cell bank. 564. The method of embodiment 563, further comprising preparing the working cell bank by the method of any one of embodiments 355 to 449. 565. The method of embodiment 563 or embodiment 564, wherein the working cell bank is prepared from a master cell bank. 566. The method of embodiment 565, further comprising preparing the master cell bank by the method of any one of embodiments 258 to 354. 567. The method of embodiment 565 or embodiment 566, wherein the master cell bank is prepared from a seed bank. 568. The method of embodiment 567, further comprising preparing the seed bank by the method of any one of embodiments 167 to 257.569. A method of producing a genomically stabilized population of PSCs, comprising culturing cells from a PSC cell population and their progeny under expansion conditions until a genomically stabilized population of PSCs is produced, wherein the expansion conditions comprise one or more or all of (a) culturing cells from the PSC cell population and their progeny in the presence of a laminin moiety and optionally in the absence of one, any two or all three of a vitronectin (e.g., in the absence of VTN-1 and / or VTN-2), a cadherin (e.g., in the absence of e-cadherin) and a feeder cell layer; (b) culturing cells from the PSC cell population and their progeny on a substrate treated for PSC adherence; and (c) clump passaging cells between different phases of expansion; thereby producing a genomically stabilized population of PSCs. 570. The method of embodiment 569, wherein the expansion conditions comprise culturing cells from the PSC cell population and their progeny in the presence of a laminin moiety and optionally in the absence of one, any two or all three of a vitronectin (e.g., in the absence of VTN-1 and / or VTN-2), a cadherin (e.g., in the absence of e-cadherin) and a feeder cell layer. 571. The method of embodiment 570, wherein the expansion conditions comprise culturing cells from the PSC cell population and their progeny in the presence of a laminin moiety as defined in any one of embodiments 108 to 129. 572. The method of any one of embodiments 569 to 571, wherein the expansion conditions comprise culturing cells from the PSC cell population and their progeny on a substrate treated for PSC adherence, optionally wherein the surface is treated for increased hydrophilicity. 573. The method of any one of embodiments 569 to 572, wherein the expansion conditions comprise clump passaging cells between different phases of expansion, optionally wherein the clump passaging conditions are as defined in any one of embodiments 30 to 55. 574. The method of any one of embodiments 569 to 573, wherein the expansion conditions comprise cultur...

Claims

WHAT IS CLAIMED IS:

1. A genomically stabilized population of pluripotent stem cells (PSCs) descended from an ancestral cell population.

2. The genomically stabilized population of claim 1, which is the progeny of at least 3 (e.g., 3) cell passages in culture from the ancestral cell population.

3. The genomically stabilized population of claim 1 or claim 2, which is the progeny of up to 50 passages in culture from the ancestral cell population.

4. The genomically stabilized population of any one of claims 1 to 3, wherein at least half the passages from the ancestral cell population are clump passages.

5. The genomically stabilized population of claim 4, wherein the clump passages have been performed in the presence of EDTA.

6. The genomically stabilized population of claim 5, wherein the clump passages have been performed by: (a) incubating a cell culture with 0.4-0.6 mM (e.g., 0.5 mM) EDTA; (b) incubating a cell culture with EDTA at a temperature below 40°C (e.g., below 40°C and optionally at least 15°C, or below 37°C and optionally at least 15°C); (c) incubating a cell culture with EDTA for 3-50 minutes (e.g., for 5-50 minutes, 7-20 minutes or 30-45 minutes); or (d) any combination of (a)-(c).

7. The genomically stabilized population of any one of claims 1 to 6, wherein at least half the passages from the ancestral population are performed with a medium comprising CEPT (chroman 1, emricasan, polyamines, and trans-ISRIB) cocktail.

8. The genomically stabilized population of any one of claims 1 to 7, wherein at least half the passages from the ancestral population are performed with a medium comprising heat-stabilized fibroblast growth factor 2 (FGF2), basic fibroblast growth factor (e.g., rh bFGF), transforming growth factor beta (e.g., rh TGFβ), or a combination thereof.

9. The genomically stabilized population of any one of claims 1 to 8, which is the progeny of at least 2 expansions in culture.

10. The genomically stabilized population of claim 9, wherein a majority of phases of a majority of expansions have been performed in the presence of at least one laminin moiety.

11. The genomically stabilized population of claim 9 or claim 10, wherein a majority of (optionally all) phases of a majority of (optionally all) expansions have been performed on an adherent surface.

12. The genomically stabilized population of any of claims 1 to 11, in which (a) the prevalence of a mutant BCL6 Corepressor (“BCOR”) gene having a c.572G>A mutation relative to the nucleotide sequence of SEQ ID NO:40 (“SNP1”) is less than 1% in the population and / or (b) (i) the population is a male cell population and the BCOR SNP1 VAF is less than 1% or (ii) the population is a female cell population and the BCOR SNP1 VAF is less than 1%.

13. The genomically stabilized population of any of claims 1 to 12, in which (a) the prevalence of a mutant BCOR gene having a c.4819+1G>A mutation relative to the nucleotide sequence of SEQ ID NO:40 (“BCOR SNP2”) is less than 1% in the population and / or (b) (i) the population is a male cell population and the BCOR SNP2 VAF is less than 1% or (ii) the population is a female cell population and the BCOR SNP2 VAF is less than 1%.

14. The genomically stabilized population of any one of claims 1 to 13, which is a population of induced pluripotent stem cells (iPSCs).

15. A method of producing a seed cell bank comprising a genomically stabilized population of PSCs, comprising: (a) expanding one or more cells of an ancestral cell population in culture in the presence of a laminin moiety under conditions in which a genomically stabilized population of PSCs is produced; (b) dispensing genomically stabilized population of PSCs produced in step (a) into cryopreservation containers; and (c) subjecting the cryopreservation containers to cryopreservation conditions, thereby producing a seed cell bank.

16. A method of producing a seed cell bank comprising a genomically stabilized population of PSCs, comprising: (a) expanding one or more cells of an ancestral cell population in culture in the presence of one or more supplements, e.g., one or more cell protection supplements, under conditions in which a genomically stabilized population of PSCs is produced;(b) dispensing genomically stabilized population of PSCs produced in step (a) into cryopreservation containers; and (c) subjecting the cryopreservation containers to cryopreservation conditions, thereby producing a seed cell bank.

17. The method of claim 16, wherein the one or more cell protection supplements comprises CEPT cocktail.

18. The method of claim 16 or claim 17, wherein step (a) is performed in the presence of a laminin moiety.

19. The method of any one of claims 15 to 18, wherein at least half the passages from the ancestral cell population are clump passages.

20. The method of claim 19, wherein the clump passages are performed in the presence of EDTA.

21. The method of claim 20, wherein the clump passages are performed by: (a) incubating a cell culture with 0.4-0.6 mM (e.g., 0.5 mM) EDTA; (b) incubating a cell culture with EDTA at a temperature below 40°C (e.g., below 40°C and optionally at least 15°C, or below 37°C and optionally at least 15°C); (c) incubating a cell culture with EDTA for 3-50 minutes (e.g., for 5-50 minutes, 7-20 minutes or 30-45 minutes); or (a) any combination of (a)-(c).

22. The method of any one of claims 15 to 22, wherein (a) the prevalence of BCOR SNP1 is less than 1% in the population of cells in the seed cell bank and / or (b) (i) population of cells in the seed cell bank is a male cell population and the BCOR SNP1 VAF is less than 1% or (ii) population of cells in the seed cell bank is a female cell population and the BCOR SNP1 VAF is less than 1%.

23. The method of any one of claims 15 to 23, wherein (a) the prevalence of BCOR SNP2 is less than 1% in the population of cells in the seed cell bank and / or (b) (i) population of cells in the seed cell bank is a male cell population and the BCOR SNP2 VAF is less than 1% or (ii) population of cells in the seed cell bank is a female cell population and the BCOR SNP2 VAF is less than 1%.

24. A method of producing a master cell bank comprising a genomically stabilized population of PSCs, comprising: (a) expanding one or more cells of a seed cell bank in culture in the presence of a laminin moiety under conditions in which a genomically stabilized population of PSCs is produced; (b) dispensing genomically stabilized population of PSCs produced in step (a) into cryopreservation containers; and (c) subjecting the cryopreservation containers to cryopreservation conditions, thereby producing a master cell bank.

25. A method of producing a master cell bank comprising a genomically stabilized population of PSCs, comprising: (a) expanding one or more cells of a seed cell bank in culture in the presence of one or more supplements, e.g., one or more cell protection supplements, under conditions in which a genomically stabilized population of PSCs is produced; (b) dispensing genomically stabilized population of PSCs produced in step (a) into cryopreservation containers; and (c) subjecting the cryopreservation containers to cryopreservation conditions, thereby producing a master cell bank.

26. The method of claim 25, wherein the one or more cell protection supplements comprises CEPT cocktail.

27. The method of claim 25 or claim 26, wherein step (a) is performed in the presence of a laminin moiety.

28. The method of any one of claims 24 to 27, wherein at least half the passages from the cell population of the seed cell bank are clump passages.

29. The method of claim 28, wherein the clump passages are performed in the presence of EDTA.

30. The method of claim 29, wherein the clump passages are performed by: (a) incubating a cell culture with 0.4-0.6 mM (e.g., 0.5 mM) EDTA;(b) incubating a cell culture with EDTA at a temperature below 40°C (e.g., below 40°C and optionally at least 15°C, or below 37°C and optionally at least 15°C); (c) incubating a cell culture with EDTA for 3-50 minutes (e.g., for 5-50 minutes, 7-20 minutes or 30-45 minutes); or (d) any combination of (a)-(c).

31. A method of producing a working cell bank comprising a genomically stabilized population of PSCs, comprising: (a) expanding one or more cells of a master cell bank in culture in the presence of a laminin moiety under conditions in which a genomically stabilized population of PSCs is produced; (b) dispensing genomically stabilized population of PSCs produced in step (a) into cryopreservation containers; and (c) subjecting the cryopreservation containers to cryopreservation conditions, thereby producing a working cell bank.

32. A method of producing a working cell bank comprising a genomically stabilized population of PSCs, comprising: (a) expanding one or more cells of a master cell bank in culture in the presence of a one or more supplements, e.g., one or more cell protection supplements under conditions in which a genomically stabilized population of PSCs is produced; (b) dispensing genomically stabilized population of PSCs produced in step (a) into cryopreservation containers; and (c) subjecting the cryopreservation containers to cryopreservation conditions, thereby producing a working cell bank 33. The method of claim 32, wherein the one or more cell protection supplements comprises CEPT cocktail.

34. The method of claim 32 or claim 33, wherein step (a) is performed in the presence of a laminin moiety.

35. The method of any one of claims 31 to 34, wherein at least half the passages from the cell population of the master cell bank are clump passages.

36. The method of claim 35, wherein the clump passages are performed in the presence of EDTA.

37. The method of claim 36, wherein the clump passages are performed by: (a) incubating a cell culture with 0.4-0.6 mM (e.g., 0.5 mM) EDTA; (b) incubating a cell culture with EDTA at a temperature below 40°C (e.g., below 40°C and optionally at least 15°C, or below 37°C and optionally at least 15°C); (c) incubating a cell culture with EDTA for 3-50 minutes (e.g., for 5-50 minutes, 7-20 minutes or 30-45 minutes); or (d) any combination of (a)-(c).

38. A method of producing an expanded pluripotent intermediate cell bank comprising a genomically stabilized population of PSCs, comprising: (a) expanding one or more cells of a working cell bank in culture in the presence of a laminin moiety under conditions in which a genomically stabilized population of PSCs is produced; (b) dispensing genomically stabilized population of PSCs produced in step (a) into cryopreservation containers; and (c) subjecting the cryopreservation containers to cryopreservation conditions, thereby producing an intermediate cell bank.

39. A method of producing an expanded pluripotent intermediate cell bank comprising a genomically stabilized population of PSCs, comprising: (a) expanding one or more cells of a working cell bank in culture in the presence of one or more supplements, e.g., cell protection supplements, under conditions in which a genomically stabilized population of PSCs is produced; (b) dispensing genomically stabilized population of PSCs produced in step (a) into cryopreservation containers; and (c) subjecting the cryopreservation containers to cryopreservation conditions, thereby producing an intermediate cell bank.

40. The method of claim 39, wherein the one or more cell protection supplements comprises CEPT cocktail.

41. The method of claim 39 or claim 40, wherein step (a) is performed in the presence of a laminin moiety.

42. The method of any one of claims 38 to 41, wherein at least half the passages from the cell population of the working cell bank are clump passages.

43. The method of any one of claims 38 to 42, wherein the clump passages are performed in the presence of EDTA.

44. The method of claim 43, wherein the clump passages are performed by: (a) incubating a cell culture with 0.4-0.6 mM (e.g., 0.5 mM) EDTA; (b) incubating a cell culture with EDTA at a temperature below 40°C (e.g., below 40°C and optionally at least 15°C, or below 37°C and optionally at least 15°C); (c) incubating a cell culture with EDTA for 3-50 minutes (e.g., for 5-50 minutes, 7-20 minutes or 30-45 minutes); or (d) any combination of (a)-(c).

45. The method of any one of claims 15 to 44, wherein the expanding of step (a) is performed in a culture medium comprising heat-stabilized fibroblast growth factor 2 (FGF2), basic fibroblast growth factor (e.g., rh bFGF), transforming growth factor beta (e.g., rh TGFβ), or a combination thereof.

46. A method of producing a genomically stabilized population of PSCs, comprising culturing cells from a PSC cell population and their progeny under expansion conditions until a genomically stabilized population of PSCs is produced, wherein the expansion conditions comprise one or more or all of (a) culturing cells from the PSC cell population and their progeny in the presence of a laminin moiety and optionally in the absence of one, any two or all three of a vitronectin (e.g., in the absence of VTN-1 and / or VTN-2), a cadherin (e.g., in the absence of e-cadherin) and a feeder cell layer;(b) culturing cells from the PSC cell population and their progeny on a substrate treated for PSC adherence; and (c) clump passaging cells between different phases of expansion; thereby producing a genomically stabilized population of PSCs.

47. A method of producing a genomically stabilized population of PSCs, comprising culturing cells from a PSC cell population and their progeny under expansion conditions until a genomically stabilized population of PSCs is produced, wherein the expansion conditions comprise (a) culturing cells from the PSC cell population and their progeny in the presence of a laminin moiety and optionally in the absence of one, any two or all three of a vitronectin (e.g., in the absence of VTN-1 and / or VTN-2), a cadherin (e.g., in the absence of e-cadherin) and a feeder cell layer; and (b) clump passaging cells between different phases of expansion; thereby producing a genomically stabilized population of PSCs.

48. The method of claim 46 or claim 47, wherein the expansion conditions comprise culturing cells from the PSC cell population and their progeny in the presence of CEPT cocktail.

49. The method of any one of claims 46 to 48, wherein the genomically stabilized population of PSCs has reduced BCOR variant frequency as compared to the PSC cell population.

50. A storage container comprising at least 50 cryopreservation containers, each containing: (a) a genomically stabilized population of PSCs of any one of claims 1 to 14; and (b) a cryopreservative.

51. A method of determining whether a PSC population (e.g., descended from an ancestral cell population) is a genomically stabilized population of PSCs, the method comprising: (a) preparing a sample from the PSC population; (b) testing the sample for the prevalence of one or more markers of tumorigenic potential; and(c) determining whether the prevalence of one or more markers of tumorigenic potential is below a threshold amount, thereby determining whether the PSC population is a genomically stabilized population of PSCs.

52. The method of claim 51, wherein the one or more markers of tumorigenic potential comprise a mutant BCOR gene.

53. A method of producing a differentiated cell population suitable for therapy, comprising culturing the genomically stabilized population of PSCs of any one of claims 1 to 14 under conditions in which the differentiated cell population is produced.

54. A method of producing a differentiated cell product suitable for therapy: (a) determining whether a PSC population is a genomically stabilized population of PSCs according to the method of claim 51 or claim 52; (b) if the PSC population is a genomically stabilized population of PSCs, then culturing cells from the genomically stabilized population of PSCs under conditions in which a differentiated cell population is produced; and (c) formulating the differentiated cell population with a pharmaceutically acceptable carrier or excipient, thereby producing a differentiated cell product suitable for therapy.

55. A method of producing a differentiated cell product suitable for therapy: (a) determining whether a PSC population is a genomically stabilized population of PSCs according to the method of claim 51 or claim 52; (b) if the PSC population is not a genomically stabilized population of PSCs, then culturing cells from the PSC cell population and their progeny under expansion conditions until a genomically stabilized population of PSCs is produced, optionally wherein the expansion conditions comprise one or more or all of: (i) culturing cells from the PSC cell population and their progeny in the presence of a laminin moiety and optionally in the absence of one, any two or all three of a vitronectin (e.g., in the absence of VTN-1 and / or VTN-2), a cadherin (e.g., in the absence of e- cadherin) and a feeder cell layer;(ii) culturing cells from the PSC cell population and their progeny on a substrate treated for PSC adherence; and (iii) clump passaging cells between different phases of expansion; (c) culturing cells from the genomically stabilized population of PSCs under conditions in which a differentiated cell population is produced; and (d) formulating the differentiated cell population with a pharmaceutically acceptable carrier or excipient, thereby producing a differentiated cell product suitable for therapy.

56. A method of producing a differentiated cell product suitable for therapy, comprising: (a) culturing the genomically stabilized population of PSCs of any one of claims 1 to 14 under conditions in which a differentiated cell population is produced; and (b) formulating the differentiated cell population with a pharmaceutically acceptable carrier or excipient, thereby producing a differentiated cell product suitable for therapy.

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