26 results about "KLF4" patented technology

The invention provides a method for improving stem cell dryness of mesenchymal stem cells and a compound and a composition thereof, the method for improving the stem cell dryness of the mesenchymal stem cells comprises the following steps: treating the mesenchymal stem cells with an active substance, activating an integrin-FAK-Src pathway, enhancing the phosphorylation level of FAK and Src proteins, and further activating a downstream PI3K / Akt pathway, so that the stem cell dryness of the mesenchymal stem cells is improved, and the stem cell dryness of the mesenchymal stem cells is improved. The cell dryness of the mesenchymal stem cells is improved. The research confirms that the COL21 has a promoting effect on MSC proliferation, and meanwhile, the COL21 is confirmed to promote expression of four stemness markers including Oct-4, Klf4, Nanog and Sox2 in MSC, so that the stemness of MSC stem cells is improved.

Provided herein are engineered nucleic acids (e.g., expression vectors, including viral vectors, such as lentiviral vectors, adenoviral vectors, AAV vectors, herpes viral vectors, and retroviral vectors) that encode OCT4; KLF4; SOX2; or any combination thereof that are useful, for example, in inducing cellular reprogramming, tissue repair, tissue regeneration, organ regeneration, reversing aging, or any combination thereof. Also provided herein are recombinant viruses (e.g., lentiviruses, alphaviruses, vaccinia viruses, adenoviruses, herpes viruses, retroviruses, or AAVs) comprising the engineered nucleic acids (e.g., engineered nucleic acids), engineered cells, compositions comprising the engineered nucleic acids, the recombinant viruses, engineered cells, engineered proteins, chemical agents that are capable of activating expression of OCT4; KLF4; SOX2; or any combination thereof, an engineered protein selected from the group consisting of OCT4; KLF4; SOX2; or any combination thereof, an antibody capable of activating expression of OCT4; KLF4; SOX2; or any combination thereof, and methods of treating a (e.g., ocular disease), preventing a disease (e.g., ocular disease), regulating (e.g., inducing or inducing and then stopping) cellular reprogramming, regulating tissue repair, regulating tissue regeneration, or any combination thereof).

Provided in the present invention are a polypeptide and composition for use in cell rejuvenation, and the use thereof. Provided are a novel truncated c-Myc factor, a novel truncated OCT4 factor, a novel truncated SOX2 factor, and a novel truncated KLF4 factor. Further provided is a truncated-OSKM composition for use in the rejuvenation of cells, tissues, or organs in a subject. The composition comprises the truncated c-Myc factor and one or more factors selected from the OCT4 factor, the SOX2 factor, and the KLF4 factor. The truncated-OSKM composition provided in the present invention not only retains the aging reprogramming ability of original OSKM, but also significantly reduces the gene length thereof and the risk of iPSC formation.

Improved compositions and methods for producing iPSCs are needed. [Solution] This specification provides a recombinant circular RNA comprising at least one protein-coding nucleic acid sequence, wherein the protein-coding nucleic acid sequence encodes a reprogramming factor (e.g., a transcription factor), and the reprogramming factor is Oct3 / 4, Klf4, Sox2, Nanog, Lin28, c-Myc, or L-Myc, or a fragment or variant thereof. This specification also provides a method for producing induced pluripotent stem cells (iPSCs), comprising contacting somatic cells with at least one of the recombinant circular RNAs described herein and maintaining the cells under conditions that will result in reprogrammed iPSCs.

The invention discloses a skin cell anti-aging composition based on regulation and control of KLF4 / UCP2 multiple pathways and application of the skin cell anti-aging composition. The skin cell anti-aging composition comprises quercetin and L-serine in a specific proportion. The application of the composition comprises various cosmetic or dermatologically acceptable dosage forms. The combination of quercetin and L-serine produces a remarkable synergistic effect, and particularly, the effect of the composition is remarkably superior to that of a single component in the aspects of inhibiting KLF4 expression so as to up-regulate UCP2 expression and eliminating ROS (reactive oxygen species). By inhibiting the expression of KLF4, the expression of UCP2 is efficiently up-regulated, and the mechanism simultaneously intervenes from the two aspects of upstream regulation of signal transduction and material basis of metabolic reaction, so that the effect is more fundamental, and the synergistic effect is remarkable. The generation of mitochondrial ROS is reduced from the source; meanwhile, by supplementing the GSH to synthesize the precursor L-serine, an endogenous anti-oxidation defense network taking the GSH as a core is enhanced, and systematic improvement of the cell anti-oxidation capability is realized.

The invention provides herein epigenomic changes identified in old mice compared to young mice or old mice treated with Oct4, Sox2, Klf4 and c-Myc (OSKM). The invention further provides methods of identifying a compound by analyzing one or more PRC2-associated epigenomic change in a sample before and after contacting the sample with one or more compounds. Also provided herein are methods of using compounds identified using the methods described herein for improving proliferative capacity, cell and tissue regeneration, and / or reducing fibrosis.

The invention belongs to the technical field of biomedical engineering, and particularly relates to an induction system for improving somatic cell reprogramming efficiency and a reprogramming method. The induction system comprises a carrier for expressing Oct4, Sox2 and Klf4 transcription factors, and sulforaphane. According to the induction system, on the basis of a classical four-factor reprogramming system, a c-Myc factor with a tumorigenic risk is removed, only Oct4, Sox2 and Klf4 three-factor expression vectors are reserved, and a natural antioxidant sulforaphane with the concentration of 2 [mu] M is innovatively introduced, so that the tumorigenic hidden danger caused by c-Myc is fundamentally avoided, the safety pain point of a traditional four-factor system is solved, and the induction system has the advantages of being simple in structure and convenient to operate. And by adding the sulforaphane, the reprogramming efficiency of the MEFs to the pluripotent iPSCs is improved by 6 times, and the high efficiency of reprogramming is realized.

The application discloses application of a substance with increased OSKM content or activity in preventing joint cartilage aging and treating osteoarthritis diseases. The OSKM of the application is obtained by connecting Oct4, Sox2, Klf4 and C-Myc. The experiment of the application proves that the OSKM or the substance with increased OSKM content or activity has a definite effect in preventing joint cartilage aging and treating osteoarthritis diseases, the application provides a new strategy for developing gene therapy for preventing joint cartilage aging and treating osteoarthritis diseases, and expands the selectable range of clinical gene therapy and drug therapy.

The invention relates to the field of molecular biology, in particular to Down's syndrome induced pluripotent stem cells as well as a construction method and application thereof. Four transcription factor reprogramming methods of KLF4, OCT4, c-MYC and SOX2 are utilized to construct Down's syndrome induced pluripotent stem cells, an expression profile of non-coding RNA in derived exosomes of the Down's syndrome induced pluripotent stem cells is systematically analyzed, differentially expressed non-coding RNA is screened, an RT-ddPCR technology is further adopted to analyze the expression condition of the differentially expressed non-coding RNA in maternal peripheral blood, and the DDown's syndrome induced pluripotent stem cells are obtained. And new information is provided for screening of novel markers for antenatal diagnosis of Down's syndrome and establishment of a detection method.

Provided herein are engineered nucleic acids (e.g., expression vectors, including viral vectors, such as lentiviral vectors, adenoviral vectors, AAV vectors, herpes viral vectors, and retroviral vectors) that encode OCT4; KLF4; SOX2; or any combination thereof that are useful, for example, in inducing cellular reprogramming, tissue repair, tissue regeneration, organ regeneration, reversing aging, or any combination thereof. Also provided herein are recombinant viruses (e.g., lentiviruses, alphaviruses, vaccinia viruses, adenoviruses, herpes viruses, retroviruses, or AAVs) comprising the engineered nucleic acids (e.g., engineered nucleic acids), engineered cells, compositions comprising the engineered nucleic acids, the recombinant viruses, engineered cells, engineered proteins, chemical agents that are capable of activating expression of OCT4; KLF4; SOX2; or any combination thereof, an engineered protein selected from the group consisting of OCT4; KLF4; SOX2; or any combination thereof, an antibody capable of activating expression of OCT4; KLF4; SOX2; or any combination thereof, and methods of treating a (e.g., ocular disease), preventing a disease (e.g., ocular disease), regulating (e.g., inducing or inducing and then stopping) cellular reprogramming, regulating tissue repair, regulating tissue regeneration, or any combination thereof).

The invention presented herein introduces a pioneering method for reprogramming somatic cells into pluripotent states through the application of cfChPs isolated from human serum. The method comprises isolating cell-free chromatin particles (cfChPs) from human serum samples; and treating the somatic cells to induce pluripotency. Induced pluripotent stem cells (iPSCs), are characterized by up regulation of stem cell related transcription factors, namely, OCT4, SOX2, KLF4 and NANOG genes; increased expression of stem cell surface markers, namely, CD34, CD44, and CD133, formation of spheroids; and teratoma formation in mice. The innovative utilization of cfChPs for reprogramming somatic cells into iPSCs represents a transformative leap in stem cell production. This approach has the potential to revolutionize regenerative medicine, disease modeling, and drug discovery, paving the way for a new era of personalized and effective therapies.

A senescence reprogramming composition and methods of use thereof, kits containing the composition, and their use in tissue repair, tissue regeneration, organ regeneration, reversal of senescence, or any combination thereof. In particular, SOX1, SOX2, SOX3, RCOR2, GMNN, GATA1, GATA2, GATA3, GATA4, GATA6, FOXA2, SOX7, SOX17, NKX3.1, NR5A2, C / EBP alpha, OCT4, PAX1, Klf4, Klf2, GLIS1 and c-MYC are used as inducible factors for reprogramming cells, tissues or organs to a young state. Compositions in the form of engineered nucleic acids, engineered cells, engineered proteins, chemical agents, or any combination thereof are provided for treating disease, preventing disease, modulating tissue repair, modulating tissue regeneration, or any combination thereof.

The application discloses a preparation method of cat induced pluripotent stem cells, which comprises the following steps: constructing piggyBac transposon plasmids carrying cat source OCT4, SOX2, KLF4 and c-MYC four factors in series, piggyBac transposon plasmids carrying cat source or pig source NANOG and LIN28 two factors in series and piggyBac transposon plasmids carrying monkey kidney virus SV40LT plasmids, and transfecting the plasmids into cat fetal fibroblasts; picking up cloned cells with embryonic stem cell morphologies, and carrying out subculture of cell clones meeting the characteristics of embryonic stem cells through identification and screening, so that the cat induced pluripotent stem cells are obtained. The preparation method of the cat induced pluripotent stem cells is safe, efficient and has good differentiation potential, lays a scientific foundation for researching in-vitro culture conditions of feline ESCs and establishment of feline iPSCs, and lays a scientific foundation for further cultivating cloned cats and gene modified cats and researching in related disease mechanisms, screening drugs and regeneration and repair.

This invention provides a method for producing induced pluripotent stem cells. [Solution] The present disclosure includes the step of producing induced pluripotent stem cells by expressing exogenous nucleic acids encoding proteins OCT3 / 4, SOX2, KLF4, LIN28, and L-MYC, as well as p53-shRNA, in umbilical cord amniotic stem cells under conditions suitable for reprogramming stem cells. The present disclosure also includes the induced pluripotent stem cell population obtainable by this method, the induced pluripotent stem cell population obtained by this method, a pharmaceutical composition containing the induced pluripotent stem cells of the present invention, a method for differentiating the induced pluripotent stem cells of the present invention, a pharmaceutical composition containing the differentiated induced pluripotent stem cells obtained by this method, and a method for treating congenital or acquired degenerative disorders in a subject, comprising the step of administering target cells differentiated from pluripotent stem cells to the subject.

The present disclosure provides compositions and methods for treating or preventing ischemic optic neuropathy with gene therapy vectors that deliver nucleic acid sequences encoding octamer-binding transcription factor 4 (OCT4), sex-determining region (Y)-box 2 (SOX2), and Krüppel-like factor 4 (KLF4). In particular, non-arteritic anterior ischemic optic neuropathy (NAION) can be treated or prevented.

The invention provides a novel nasal mucosa-derived pluripotent stem cell, a separation method and application, and belongs to the technical field of stem cell biotechnology and tissue engineering. According to the method, the technical scheme of'no enzyme digestion + continuous two-stage factor induction + three-dimensional sphere screening 'is creatively adopted, and the novel nasal mucosa-derived pluripotent stem cells are efficiently separated and enriched from nasal mucosa tissues. The method is simple to operate, reduces the risk of cell injury, can accurately screen out novel nasal mucosa-derived pluripotent stem cells expressing CD109 + and CD55 + surface markers and Nanog / Oct4 / Sox2 / Klf4 pluripotent core transcription factors, and solves the problems of low purity and instable dryness in the traditional method. Meanwhile, the nasal mucosa tissue is convenient to obtain, trauma is small, and compared with BMSCs (bone marrow mesenchymal stem cells) needing bone marrow puncture and ADMSCs (adipose mesenchymal stem cells) needing liposuction, the clinical application threshold is greatly lowered.

An aging reprogramming composition, a use method therefor, a kit containing the composition, and the use of the composition in tissue repair, tissue regeneration, organ regeneration, aging reversion, or any combination thereof. The present invention relates to SOX1, SOX2, SOX3, RCOR2, GMNN, GATA1, GATA2, GATA3, GATA4, GATA6, FOXA2, SOX7, SOX17, NKX3.1, NR5A2, C / EBPα, OCT4, PAX1, Klf4, Klf2, GLIS1 and c-MYC, which are used as inducing factors to reprogram cells, tissues or organs to restore a youthful state. Provided is a composition of an activation inducing factor in the form of an engineered nucleic acid, an engineered cell, an engineered protein, a chemical agent, or any combination thereof, wherein the composition is used for treating diseases, preventing diseases, modulating tissue repair, modulating tissue regeneration, or any combination thereof.

The application provides a quantitative epigenetic reprogramming method, reagents and application thereof in reversing organ fibrosis drugs, and belongs to the technical field of biological medicines.The epigenetic age of cells is reduced by 57%-77% by a gene reprogramming method; the gene reprogramming method is that mRNA sequences coding OCT4, SOX2, KLF4 and GLIS1 are delivered to cells for 2-3 weeks, and expression is induced by doxycycline for 1-2 weeks. The application solves the industry problem that reprogramming cannot be carried out in vivo by a quantitative epigenetic partial reprogramming strategy, reverses pathological cells to functional or resting state cells without changing the cell identity, and is not a pluripotent stem cell, thereby solving the industry problem that reprogramming cannot be carried out in vivo, realizing safe reversal of fibrosis in an animal model, and significantly reducing the epigenetic age, and reversing a disease that was once incurable.

Provided herein are compositions and methods for preventing ocular vascular regression, preserving visual function, or both, comprising: identifying a subject in need of treatment for ocular vascular regression; and providing the subject with an effective amount of an agent that is: an agonist that increases expression of at least one gene selected from: ETS-Related Gene (ERG), Fli-1 Proto-Oncogene; ETS Transcription Factor (FLU); KEF transcription factor 2 (KLF2); KEF transcription factor 4 (KLF4); or a Piezo-Type Mechanosensitive Ion Channel Component 1 (PIEZO1) agonist, or both; wherein the agent is provided in an amount sufficient to prevent the ocular vascular regression, preserving visual function, or both.

Provided herein are engineered nucleic acids (e.g., expression vectors, including viral vectors, such as lentiviral vectors, adenoviral vectors, AAV vectors, herpes viral vectors, and retroviral vectors) that encode OCT4; KLF4; SOX2; or any combination thereof that are useful, for example, in inducing cellular reprogramming, tissue repair, tissue regeneration, organ regeneration, reversing aging, or any combination thereof. Also provided herein are recombinant viruses (e.g., lentiviruses, alphaviruses, vaccinia viruses, adenoviruses, herpes viruses, retroviruses, or AAVs) comprising the engineered nucleic acids (e.g., engineered nucleic acids), engineered cells, compositions comprising the engineered nucleic acids, the recombinant viruses, engineered cells, engineered proteins, chemical agents that are capable of activating expression of OCT4; KLF4; SOX2; or any combination thereof, an engineered protein selected from the group consisting of OCT4; KLF4; SOX2; or any combination thereof, an antibody capable of activating expression of OCT4; KLF4; SOX2; or any combination thereof, and methods of treating a (e.g., ocular disease), preventing a disease (e.g., ocular disease), regulating (e.g., inducing or inducing and then stopping) cellular reprogramming, regulating tissue repair, regulating tissue regeneration, or any combination thereof).

The invention relates to application of KLF4 as a target spot in APOE4 genotype Alzheimer disease, and belongs to the technical field of biological medicine. The invention provides an application of KLF4 in preparation of any one of the following medicines: (1) improving learning and memory ability impairment; (2) the blood-brain barrier function is improved; and (3) treating or preventing neurodegenerative diseases. According to the application disclosed by the invention, the expression of KLF4 in cerebral cortex of APOE4 genotype patients and mice is obviously reduced, the KLF4 in APOE4 mice is obviously lower than that in APOE3 mice, and the cortex expression of APOE4 carriers is lower than that of non-carriers. According to the application disclosed by the invention, in-depth research by taking the KLF4 as an entry point finds that the APOE4 reduces the expression of the KLF4 and destroys a BBB structure, so that learning and memory impairment is caused, and then the APOE4 develops into neurodegenerative diseases, and the symptoms can be improved by overexpression of the KLF4.

The present disclosure relates to vectors, compositions, pharmaceutical compositions and kits providing brain cell-specific expression of reprogramming genes, such as Yamanaka factors Oct4, Sox2, Klf4 and c-Myc (OSKM). Methods and uses including the same for treating Alzheimer's disease and progeria by brain cell-specific expression of reprogramming genes, such as OSKM, are also provided.

The disclosure is directed to methods of generating induced pluripotent Procavia capensis stem cells that combine transfection and chemical reprogramming. Specifically, the disclosure provides methods of generating induced pluripotent P. capensis stem cells that include generating primed P. capensis cells by chemically reprogramming primary P. capensis cells transfected with OCTA. 80X2. KI.F4. CMYC. and GLIS1 by culturing the cells, generating pre-induced P. capensis cells from the primed P. capensis cells by transfecting the primed P. capensis cells with OCT4. 80X2. KLF4, CMYC, and NANOG and culturing these cells, and generating the induced pluripotent P. capensis stem cells from the pre-induced P. capensis cells by transfecting the pre-induced P. capensis cells with OCT4, SOX2, KLF4. CMYC, NANOG, IJN28A. and SV40 and culturing the transfected cells. In other embodiments, the primary P. capensis cells are cultured to generate pre-induced P. capensis cells, which are then transfected with at least OCT4ISOX2IKLF4ICMYC. and SV40 T-antigen or an shRNA targeting TP53 and cultured again. The culturing uses a culture medium supplemented with an HD AC inhibitor, a GSK-3 inhibitor, a monoamine oxidase inhibitor, an activator of eukaryotic adenylyl cyclase, a retinoid, a DOT1L inhibitor, and a TGF-β inhibitor. The disclosure is also directed to cell culture media useful in such methods and induced pluripotent P. capensis stem cells expressing at least OCT4, 80X2, KLF4, CMYC, NANOG, LIN28A, and SV40.

The application provides a transcription factor capable of regulating the function of an IGF2BP1 gene and an application, and researches find that a rs640807869 (C>G) site changes the expression efficiency of IGF2BP1 by affecting the binding of transcription factors SP1 and KLF4 to an IGF2BP1 DNA fragment; the site is significantly related to the chest circumference of Nanjiang yellow sheep and can be used as one of potential sites for breeding Nanjiang yellow sheep. SP1 can promote the proliferation and differentiation of goat MuSCs, and the function of KLF4 is opposite to that of SP1, and the function of the rs640807869 (C>G) site is closely related to the two transcription factors, and the proliferation and differentiation of goat MuSCs can be affected by regulating the two transcription factors.

Provided are methods for treating a subject with a liver disease such as metabolic dysfunction-associated steatotic liver disease (MASLD) or metabolic dysfunction-associated steatohepatitis (MASH). The method may include administering to the subject one or more nucleic acids encoding OCT4, SOX2 and KLF4. The administration may rejuvenate hepatocytes or liver stellate cells in the subject, and may improve a symptom of the liver disease.

The present invention provides in vitro methods for producing an endothelial cell with blood-brain barrier (BBB)-like properties. The methods include culturing an endothelial cell in a medium comprising a Wnt / β-catenin signaling activator and expressing one or more transcription factors in the endothelial progenitor cells for at least 2 days. The one or more transcription factors are selected from DACH1, DACH2, FLI1, FOS, FOXC1, FOXF1, FOXF2, FOXQ1, HES1, JUN, KLF2, KLF4, LEF1, MECOM, NR4A1, NR4A2, PPARD, TBX3, TSC22D1, ZIC2, ZIC3 and combinations thereof.