| Literature DB >> 28128194 |
Xiaoping Han1,2,3,4, Hao Yu5, Daosheng Huang1,4, Yang Xu1,4, Assieh Saadatpour6, Xia Li1,4, Lengmei Wang7, Jie Yu8, Luca Pinello6, Shujing Lai1,4, Mengmeng Jiang1,4, Xueying Tian9, Fen Zhang1, Yanhong Cen1, Yuko Fujiwara2, Wei Zhu7, Bin Zhou10, Tianhua Zhou11, Hongwei Ouyang1,3, Jianan Wang7,4, Guo-Cheng Yuan6, Shumin Duan5, Stuart H Orkin2,7, Guoji Guo1,2,3,4.
Abstract
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.Entities:
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Year: 2017 PMID： 28128194 PMCID： PMC5339836 DOI： 10.1038/cr.2017.17
Source DB: PubMed Journal: Cell Res ISSN： 1001-0602 Impact factor: 25.617