JMJD1C Ensures Mouse Embryonic Stem Cell Self-Renewal and Somatic Cell Reprogramming through Controlling MicroRNA Expression

Stem Cell Reports

卷:9

Jing Hu¹  Shuang Li¹  Junjie Gu¹  Bing Liao¹  Ying Jin²  Ming Sun²  Haixin Zhao²  Feng Xiao² 

[1] Department of Histoembryology, Genetics and Developmental Biology, Institute of Medical Sciences, Shanghai JiaoTong University School of Medicine, 225 South Chongqing Road, Shanghai 200025, China;

[2] Key Laboratory of Stem Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China;

关键词: JMJD1C;    H3K9 demethylase;    KLF4;    embryonic stem cells;    self-renewal;    reprogramming;    microRNAs;    ERK/MAPK signaling;    EMT;   

DOI  :  10.1016/j.stemcr.2017.07.013

来源: DOAJ

【 摘 要 】

The roles of histone demethylases (HDMs) for the establishment and maintenance of pluripotency are incompletely characterized. Here, we show that JmjC-domain-containing protein 1c (JMJD1C), an H3K9 demethylase, is required for mouse embryonic stem cell (ESC) self-renewal. Depletion of Jmjd1c leads to the activation of ERK/MAPK signaling and epithelial-to-mesenchymal transition (EMT) to induce differentiation of ESCs. Inhibition of ERK/MAPK signaling rescues the differentiation phenotype caused by Jmjd1c depletion. Mechanistically, JMJD1C, with the help of pluripotency factor KLF4, maintains ESC identity at least in part by regulating the expression of the miR-200 family and miR-290/295 cluster to suppress the ERK/MAPK signaling and EMT. Additionally, we uncover that JMJD1C ensures efficient generation and maintenance of induced pluripotent stem cells, at least partially through controlling the expression of microRNAs. Collectively, we propose an integrated model of epigenetic and transcriptional control mediated by the H3K9 demethylase for ESC self-renewal and somatic cell reprogramming.

【 授权许可】

Unknown