WDR5 Interaction Modulation for Serum-Free Mesodermal Cell Derivation
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Solution Overview
Problem
Current methods for deriving mesodermal lineage cells from embryonic stem cells require expensive and poorly characterized serum-containing media, leading to high variability and increased costs, and lack efficiency in generating cardiac and hematopoietic lineage cells without the need for serum or growth factors.
Innovation Solution
The method involves modulating the interaction of WDR5 protein at its binding site with RBBP5, MYC, and KANSL2 by disrupting and then re-establishing its expression in embryonic stem cells, allowing for the serum-free and growth-factor-free differentiation into mesodermal, cardiac, and hematopoietic lineage cells, and the creation of mixed tissue organoids with retinal and cardiac lineage cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If serum-containing media is used to culture embryonic stem cells for deriving mesodermal lineage cells, then cell differentiation can be achieved, but culture costs increase and composition becomes poorly characterized
Solution Approach 1:
The patent removes serum and growth factors from the culture media, extracting the problematic components that cause high costs and poor characterization. The method achieves mesodermal lineage cell differentiation using only defined化学成分 (chemical components) without serum, thereby reducing culture costs while maintaining differentiation reliability
Solution Approach 2:
The patent changes the chemical composition parameters of the culture media by eliminating serum and growth factors. This parameter change transforms the media from an undefined, expensive composition to a defined, cost-effective formulation that still supports reliable mesodermal lineage cell differentiation
2Reliability
If serum-containing media is used for mesodermal lineage cell derivation, then differentiation can proceed, but culture variability increases
Solution Approach 1:
The patent changes the media composition parameters by removing serum and growth factors, creating a defined culture system. This reduces culture variability because defined化学成分 provide consistent, reproducible conditions for mesodermal lineage cell differentiation across different batches and experiments
3Reliability
If growth factors are used to replace serum for mesodermal lineage cell derivation, then serum-free culture is achieved, but culture costs increase
Solution Approach 1:
The patent removes both serum and growth factors from the culture media, extracting the expensive components. The method demonstrates that mesodermal lineage cell differentiation can be achieved using only basic defined化学成分 without requiring costly growth factors, thereby achieving serum-free culture at reduced cost
Data Source
AI summary
The disclosure relates to methods for producing mesodermal lineage cells, cardiac lineage cells, hematopoietic lineage cells, retinal lineage cells, and combinations thereof. In some aspects, the disclosure relates to methods of producing mixed tissue organoids comprising retinal lineage cells and cardiac lineage cells. When interaction of WDR5 protein at the binding pocket/interaction surface with RBBP5/MYC/KANSL2 is disrupted in the embryonic stem cell for a set period of time after differentiation of the embryonic stem cell has begun, and the disruption of that interaction is subsequently removed, differentiation of the embryonic stem cell to a mesodermal lineage cell is obtained. Such mesodermal lineage cells may, in some methods of the disclosure, be subsequently differentiated into cardiac lineage cells and hematopoietic lineage cells. The disclosure also relates to method for producing mixed lineage organoids, comprising retinal and mesodermal, including cardiac, lineage cells in a single organoid. The disclosure also relates to cells and organoids obtained by the methods, uses of the cells and organoids, and kits comprising the cells and/or reagents for producing them.