1. The oncogene c-Jun impedes somatic cell reprogramming.
- Author
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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, and Chen, You
- Subjects
SOMATIC cells ,C-Jun N-terminal kinases regulation ,MITOGEN-activated protein kinase regulation ,ONCOGENES ,NEOPLASTIC cell transformation - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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