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Modulation of STAT3 phosphorylation by PTPN2 inhibits naïve pluripotency of embryonic stem cells
Author(s) -
Zhang Yan,
Ding Huiwen,
Wang Xiaohu,
Ye ShouDong
Publication year - 2018
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13112
Subject(s) - embryonic stem cell , microbiology and biotechnology , stat3 , leukemia inhibitory factor , phosphorylation , epiblast , induced pluripotent stem cell , tyrosine phosphorylation , stem cell , biology , chemistry , genetics , gastrulation , gene
STAT3 phosphorylation at tyrosine 705 (STAT3 pY705 ), triggered by the addition of the leukemia inhibitory factor (LIF), can maintain mouse embryonic stem cell (mESC) self‐renewal and reprogram mouse epiblast stem cells (EpiSCs) to enter a naïve pluripotent state. The activation of STAT3 pY705 occurs mainly through Janus kinases. However, it remains unclear how STAT3 pY705 levels are decreased in mESCs. Our study shows that upregulation of the protein tyrosine phosphatase (PTPN2 ) inhibits STAT3 activity by reducing its phosphorylation level and promotes mESC differentiation, whereas PTPN2 knockout by CRISPR/CAS9 delays mESC differentiation. Consistently, PTPN2 knockdown facilitates the generation of mESC‐like colonies in STAT3‐ overexpressing EpiSCs. PTPN2‐mediated STAT3 activity, thus, contributes to the exit of ESCs from the pluripotent ground state. These findings expand the current understanding of the regulatory network of naïve pluripotency.