| Literature DB >> 26098572 |
Jing Liu1, Qingkai Han1, Tianran Peng1, Meixiu Peng1, Bei Wei1, Dongwei Li1, Xiaoshan Wang2, Shengyong Yu3, Jiaqi Yang1, Shangtao Cao1, Kaimeng Huang1, Andrew Paul Hutchins2, He Liu1, Junqi Kuang3, Zhiwei Zhou1, Jing Chen1, Haoyu Wu4, Lin Guo1, Yongqiang Chen1, You Chen1, Xuejia Li1, Hongling Wu1, Baojian Liao1, Wei He1, Hong Song1, Hongjie Yao1, Guangjin Pan1, Jiekai Chen2, Duanqing Pei2.
Abstract
Oncogenic transcription factors are known to mediate the conversion of somatic cells to tumour or induced pluripotent stem cells (iPSCs). Here we report c-Jun as a barrier for iPSC formation. c-Jun is expressed by and required for the proliferation of mouse embryonic fibroblasts (MEFs), but not mouse embryonic stem cells (mESCs). Consistently, c-Jun is induced during mESC differentiation, drives mESCs towards the endoderm lineage and completely blocks the generation of iPSCs from MEFs. Mechanistically, c-Jun activates mesenchymal-related genes, broadly suppresses the pluripotent ones, and derails the obligatory mesenchymal to epithelial transition during reprogramming. Furthermore, inhibition of c-Jun by shRNA, dominant-negative c-Jun or Jdp2 enhances reprogramming and replaces Oct4 among the Yamanaka factors. Finally, Jdp2 anchors 5 non-Yamanaka factors (Id1, Jhdm1b, Lrh1, Sall4 and Glis1) to reprogram MEFs into iPSCs. Our studies reveal c-Jun as a guardian of somatic cell fate and its suppression opens the gate to pluripotency.Entities:
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Year: 2015 PMID： 26098572 DOI： 10.1038/ncb3193
Source DB: PubMed Journal: Nat Cell Biol ISSN： 1465-7392 Impact factor: 28.824