A molecular roadmap for induced multi-lineage transdifferentiation of fibroblasts by chemical combinations

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 fi...

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Published in:细胞研究：英文版 2017, Vol.27 (3), p.386-401
Main Author: Xiaoping Han Hao Yu Daosheng Huang Yang Xu Assieh Saadatpour Xia Li Lengmei Wang Jie Yu Luca Pinello Shujing Lai Mengmeng Jiang Xueying Tian Fen Zhang Yanhong Cen Yuko Fujiwara Wei Zhu Bin Zhou Tianhua Zhou Hongwei Ouyang Jianan Wang Guo-Cheng Yuan Shumin Duan Smart H Orkin Guoji Guo
Format: Article
Language:English
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Summary: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. Final- ly, 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.
ISSN:1001-0602
1748-7838