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- Title
The oncogene c-Jun impedes somatic cell reprogramming.
- Authors
Liu, Jing; Han, Qingkai; Peng, Tianran; Peng, Meixiu; Wei, Bei; Li, Dongwei; Wang, Xiaoshan; Yu, Shengyong; Yang, Jiaqi; Cao, Shangtao; Huang, Kaimeng; Hutchins, Andrew Paul; Liu, He; Kuang, Junqi; Zhou, Zhiwei; Chen, Jing; Wu, Haoyu; Guo, Lin; Chen, Yongqiang; Chen, You
- 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.
- Subjects
SOMATIC cells; C-Jun N-terminal kinases regulation; MITOGEN-activated protein kinase regulation; ONCOGENES; NEOPLASTIC cell transformation
- Publication
Nature Cell Biology, 2015, Vol 17, Issue 7, p856
- ISSN
1465-7392
- Publication type
Article
- DOI
10.1038/ncb3193