Modulation of STAT3 phosphorylation by PTPN2 inhibits naive pluripotency of embryonic stem cells
Modulation of STAT3 phosphorylation by PTPN2 inhibits naive pluripotency of embryonic stem cells
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PTPN2 调节 STAT3 磷酸化抑制胚胎干细胞的幼稚多能性
DOI：
10.1002/1873-3468.13112
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发表时间：
2018
期刊：
影响因子：
3.5
通讯作者：
Ye Shou-Dong
中科院分区：
文献类型：
--
作者：
Zhang Yan;Ding Huiwen;Wang Xiaohu;Ye Shou-Dong
通过添加白血病抑制因子（LIF）触发的STAT 3酪氨酸705磷酸化（STAT 3 pY 705）可以维持小鼠胚胎干细胞（mESC）自我更新并重新编程小鼠上胚层干细胞（EpiSC）以进入幼稚多能状态。STAT 3 pY 705的激活主要通过Janus激酶进行。然而，目前尚不清楚STAT 3 pY 705水平是如何在mESC中降低的。我们的研究表明，蛋白酪氨酸磷酸酶（PTPN 2）的上调通过降低其磷酸化水平来抑制STAT 3活性，并促进mESC分化，而通过CRISPR/CAS 9敲除PTPN 2会延迟mESC分化。一致地，PTPN 2敲低促进在STAT 3过表达的EpiSC中产生mESC样集落。因此，PTPN 2介导的STAT 3活性有助于ESC从多能基态退出。这些发现扩展了目前对幼稚多能性调控网络的理解。
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 STAT3pY705occurs mainly through Janus kinases. However, it remains unclear how STAT3pY705levels 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, whereasPTPN2knockout by CRISPR/CAS9 delays mESC differentiation. Consistently, PTPN2 knockdown facilitates the generation of mESC‐like colonies inSTAT3‐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.