STAT3 Phosphorylation at Tyrosine 705 and Serine 727 Differentially Regulates Mouse ESC Fates

被引:133
作者
Huang, Guanyi [1 ]
Yan, Hexin [1 ,2 ]
Ye, Shoudong [1 ]
Tong, Chang [1 ]
Ying, Qi-Long [1 ]
机构
[1] Univ So Calif, Keck Sch Med, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Dept Cell & Neurobiol, Los Angeles, CA 90033 USA
[2] Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Shanghai, Peoples R China
关键词
Differentiation; Phosphorylation; Embryonic stem cell; Self-renewal; STAT3; EMBRYONIC STEM-CELLS; MAMMARY-GLAND INVOLUTION; SELF-RENEWAL; SIGNAL TRANSDUCER; GROUND-STATE; PLURIPOTENCY; ACTIVATION; TRANSCRIPTION-3; COMMITMENT; NANOG;
D O I
10.1002/stem.1609
中图分类号
Q813 [细胞工程];
学科分类号
摘要
STAT3 can be transcriptionally activated by phosphorylation of its tyrosine 705 or serine 727 residue. In mouse embryonic stem cells (mESCs), leukemia inhibitory factor (LIF) signaling maintains pluripotency by inducing JAK-mediated phosphorylation of STAT3 Y705 (pY705). However, the function of phosphorylated S727 (pS727) in mESCs remains unclear. In this study, we examined the roles of STAT3 pY705 and pS727 in regulating mESC identities, using a small molecule-based system to post-translationally modulate the quantity of transgenic STAT3 in STAT3(-/-) mESCs. We demonstrated that pY705 is absolutely required for STAT3-mediated mESC self-renewal, while pS727 is dispensable, serving only to promote proliferation and optimal pluripotency. S727 phosphorylation is regulated directly by fibroblast growth factor/Erk signaling and crucial in the transition of mESCs from pluripotency to neuronal commitment. Loss of S727 phosphorylation resulted in significantly reduced neuronal differentiation potential, which could be recovered by a S727 phosphorylation mimic. Moreover, loss of pS727 sufficed LIF to reprogram epiblast stem cells to naive pluripotency, suggesting a dynamic equilibrium of STAT3 pY705 and pS727 in the control of mESC fate. Stem Cells 2014;32:1149-1160
引用
收藏
页码:1149 / 1160
页数:12
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