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外源性Nanog可缓解但不足以逆转由PI3K信号抑制诱导的胚胎干细胞分化。

Exogenous Nanog alleviates but is insufficient to reverse embryonic stem cells differentiation induced by PI3K signaling inhibition.

作者信息

Liu Na, Lu Min, Feng Xiao Ming, Ma Feng Xia, Fang Zhi Hong, Tian Xue Mei, Ren Qian, Zhang Lei, Liu Bin, Huang Ping Ping, Liu Lin, Han Zhong Chao

机构信息

State Key Laboratory of Experimental Hematology, Institute of Hematology, National Research Center for Stem Cell Engineering and Technology, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.

出版信息

J Cell Biochem. 2009 Apr 15;106(6):1041-7. doi: 10.1002/jcb.22082.

Abstract

PI3K signaling pathway plays a significant role in embryonic stem cells (ES cells) self-renewal. Overexpression of Nanog maintains mouse ES cells pluripotency independent of leukemia inhibitory factor (LIF). However, little is known about the effect of PI3K signaling pathway on ES cells with Nanog overexpression. Our experiments aimed to explore the relationship between PI3K signaling pathway and Nanog expression in ES cells. We observed the effect of LY294002, a specific inhibitor of PI3K pathway, on wild-type J1 cells and Nanog overexpressing (Ex-Nanog) J1 cells in the presence or absence of LIF. With LY294002 treatment, both of them lost their ES features even in the presence of LIF. But the differentiation induced by LY294002 on Ex-Nanog J1 cells was slighter lower than that on wild-type J1 cells. These results indicate that inhibition of PI3K pathway induces mouse ES cells differentiation. Exogenous Nanog sustains mouse ES cells pluripotency independent of LIF, and alleviates the differentiation induced by LY294002. But it is insufficient to totally reverse the differentiation.

摘要

PI3K信号通路在胚胎干细胞(ES细胞)的自我更新中起着重要作用。Nanog的过表达可维持小鼠ES细胞的多能性,且不依赖白血病抑制因子(LIF)。然而,关于PI3K信号通路对过表达Nanog的ES细胞的影响却知之甚少。我们的实验旨在探索ES细胞中PI3K信号通路与Nanog表达之间的关系。我们观察了PI3K通路特异性抑制剂LY294002在有或无LIF存在的情况下,对野生型J1细胞和过表达Nanog(Ex-Nanog)的J1细胞的作用。经LY294002处理后,即使在有LIF存在的情况下,这两种细胞均失去了其ES细胞特征。但LY294002对Ex-Nanog J1细胞诱导的分化程度略低于对野生型J1细胞的诱导分化程度。这些结果表明,抑制PI3K通路可诱导小鼠ES细胞分化。外源性Nanog可维持小鼠ES细胞的多能性,且不依赖LIF,并减轻LY294002诱导的分化。但它不足以完全逆转分化。

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