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CDK11 safeguards the identity of human embryonic stem cells via fine‐tuning signaling pathways
Author(s) -
Ding Jianyi,
Fang Zhuoqing,
Liu Xinyuan,
Zhu Zhexin,
Wen Chunsheng,
Wang Han,
Gu Junjie,
Li Qingrun,
Zeng Rong,
Li Hui,
Jin Ying
Publication year - 2020
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.29305
Subject(s) - microbiology and biotechnology , biology , signal transduction , mapk/erk pathway , embryonic stem cell , kinase , protein kinase a , phosphatase , phosphorylation , genetics , gene
Abstract Signaling pathways transmit extracellular cues into cells and regulate transcriptome and epigenome to maintain or change the cell identity. Protein kinases and phosphatases are critical for signaling transduction and regulation. Here, we report that CDK11, a member of the CDK family, is required for the maintenance of human embryonic stem cell (hESC) self‐renewal. Our results show that, among the three main isoforms of CDK11, CDK11 p46 is the main isoform safeguarding the hESC identity. Mechanistically, CDK11 constrains two important mitogen‐activated protein kinase (MAPK) signaling pathways (JNK and p38 signaling) through modulating the activity of protein phosphatase 1. Furthermore, CDK11 knockdown activates transforming growth factor β (TGF‐β)/SMAD2/3 signaling and upregulates certain nonneural differentiation‐associated genes. Taken together, this study uncovers a kinase required for hESC self‐renewal through fine‐tuning MAPK and TGF‐β signaling at appropriate levels. The kinase‐phosphatase axis reported here may shed new light on the molecular mechanism sustaining the identity of hESCs.