MEK/ERK signaling contributes to the maintenance of human embryonic stem cell self-renewal

被引:204
作者
Li, Jian [1 ]
Wang, Guangwen [1 ]
Wang, Chengyan [1 ]
Zhao, Yang [1 ]
Zhang, Hong [1 ]
Tan, Zhijia [1 ]
Song, Zhihua [1 ]
Ding, Mingxiao [1 ]
Deng, Hongkui [1 ]
机构
[1] Peking Univ, Coll Life Sci, Minist Educ, Key Lab Cell Proliferat & Differentiat, Beijing 100871, Peoples R China
基金
中国国家自然科学基金;
关键词
human embryonic stem cells; self-renewal; MEK/ERK; FGF;
D O I
10.1111/j.1432-0436.2006.00143.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
MEK/ERK signaling plays a crucial role in a diverse set of cellular functions including cell proliferation, differentiation and survival, and recently has been reported to negatively regulate mouse embryonic stem cell (mESC) self-renewal by antagonizing STAT3 activity. However, its role in human ESCs (hESCs) remains unclear. Here we investigated the functions of MEK/ERK in controlling hESC activity. We demonstrated that MEK/ERK kinases were targets of fibroblast growth factor (FGF) pathway in hESCs. Surprisingly, we found that, in contrast to mESCs, high basal MEK/ERK activity was required for maintaining hESCs in an undifferentiated state. Inhibition of MEK/ERK activity by specific MEK inhibitors PD98059 and U0126, or by RNA interference, rapidly caused the loss of self-renewal capacity. We also showed that MEK/ERK signaling cooperated with phosphoinositide 3-kinase (PI3K)/AKT signaling in maintaining hESC pluripotency. However, MEK/ERK signaling had little or no effect on regulating hESC proliferation and survival, in contrast to PI3K/AKT signaling. Taken together.. these findings reveal the unique and crucial role of MEK/ERK signaling in the determination of hESC cell fate and expand our understanding of the molecular mechanisms behind the FGF pathway maintenance of hESC pluripotency. Importantly, these data make evident the striking differences in the control of self-renewal between hESCs and mESCs.
引用
收藏
页码:299 / 307
页数:9
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