Modulation of STAT3 phosphorylation by PTPN2 inhibits naïve pluripotency of embryonic stem cells

STAT3 phosphorylation at tyrosine 705 (STAT3pY705), 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 STAT3pY705 occurs m...

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Published inFEBS letters Vol. 592; no. 13; pp. 2227 - 2237
Main Authors Zhang, Yan, Ding, Huiwen, Wang, Xiaohu, Ye, Shou‐Dong
Format Journal Article
LanguageEnglish
Published England 01.07.2018
Subjects
differentiation
embryonic stem cells
PTPN2
self‐renewal
STAT3
differentiation
self-renewal
embryonic stem cells
PTPN2
STAT3
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Summary:STAT3 phosphorylation at tyrosine 705 (STAT3pY705), 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 STAT3pY705 occurs mainly through Janus kinases. However, it remains unclear how STAT3pY705 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.
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ISSN:0014-5793
1873-3468
DOI:10.1002/1873-3468.13112