A Molecular Roadmap for Induced Multi-lineage Trans-differentiation of Fibroblasts by Chemical Combinations
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE91374 | GEO | 2017/01/17
SECONDARY ACCESSION(S): PRJNA356865
REPOSITORIES: GEO
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Project description:Recent advances have demonstrated the power of small molecules in promoting cellular reprogramming. Yet, the full potential of such chemicals in cell fate manipulation and the underlying mechanisms require further characterization. Through functional screening assays, we find that mouse embryonic fibroblast cells can be induced to trans-differentiate into a wide range of somatic lineages simultaneously by treatment with a combination of four chemicals. Genomic analysis of the process indicates activation of multi-lineage modules and relaxation of epigenetic silencing programs. In addition, we identify Sox2 as an important regulator within the induced network. Single cell analysis uncovers a novel priming state that enables transition from fibroblast cells to diverse somatic lineages. Finally, we demonstrate that modification of the culture system enables directional trans-differentiation towards myocytic, glial or adipocytic lineages. Our study describes a cell fate control system that may be harnessed for regenerative medicine.
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Project description:Recent advances highlight the power of small molecules for promoting cellular reprogramming. Yet, the full potential of such chemicals in cell fate manipulation and the underlying mechanisms needs further characterization. Through functional screening assays, we found that mouse embryonic fibroblast can be induced to trans-differentiate into a wide range of somatic lineages simultaneously by treatment with a combination of four chemicals. Genomic analysis of the process indicates activation of multi-lineage modules and relaxation of epigenetic silencing programs. In addition, we identify Sox2 as an important regulator within the induced network. Single cell analysis uncovers a priming state that enables transition from fibroblast cells to diverse somatic lineages. Finally, we demonstrate that modification of the culture system enables directional trans-differentiation towards cardiac, neuronal or adipocytic lineages. Our study describes a cell fate control system that may be harnessed for regenerative medicine.
2017-01-17 | GSE91373 | GEO
Project description:Recent advances highlight the power of small molecules for promoting cellular reprogramming. Yet, the full potential of such chemicals in cell fate manipulation and the underlying mechanisms needs further characterization. Through functional screening assays, we found that mouse embryonic fibroblast can be induced to trans-differentiate into a wide range of somatic lineages simultaneously by treatment with a combination of four chemicals. Genomic analysis of the process indicates activation of multi-lineage modules and relaxation of epigenetic silencing programs. In addition, we identify Sox2 as an important regulator within the induced network. Single cell analysis uncovers a priming state that enables transition from fibroblast cells to diverse somatic lineages. Finally, we demonstrate that modification of the culture system enables directional trans-differentiation towards cardiac, neuronal or adipocytic lineages. Our study describes a cell fate control system that may be harnessed for regenerative medicine. We used microarrays to detect the global gene expression patterns underlying induced multi-lineage trans-differentiation
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Project description:A Molecular Roadmap for Induced Multi-lineage Trans-differentiation of Fibroblasts by Chemical Combinations
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