Depletion of Tcf3 and Lef1 maintains mouse embryonic stem cell self-renewal.
Depletion of Tcf3 and Lef1 maintains mouse embryonic stem cell self-renewal.
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Tcf3和Lef1的耗竭维持小鼠胚胎干细胞的自我更新
DOI：
10.1242/bio.022426
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发表时间：
2017-04-15
期刊：
影响因子：
2.4
通讯作者：
Ying QL
中科院分区：
文献类型：
--
作者：
Ye S;Zhang T;Tong C;Zhou X;He K;Ban Q;Liu D;Ying QL
摘要小鼠和大鼠胚胎干细胞(ESC)的自我更新可以通过双重抑制糖原合成酶激酶3(GSK3)和丝裂原激活的蛋白激酶(MEK)来维持。抑制GSK3通过消除T细胞因子3(TCF3)介导的多能性网络抑制促进ESC的自我更新。然而，抑制MEK是如何介导ESC自我更新的，在很大程度上仍不清楚。在这里，我们发现抑制MEK可以显著抑制小鼠ESCs中淋巴增强因子1(LEF1)的表达。Lef1基因的敲除或敲除部分模拟了MEK抑制剂的自我更新促进作用。此外，Tcf3和Lef1的缺失能够在没有外源因素、细胞因子或抑制剂的情况下维持小鼠未分化的ESCs。转录组重测序分析表明，LEF1与ESCs的内胚层特性密切相关。因此，我们的研究支持这样一个观点，即维持ESCs基态的关键是保护ESCs免受分化线索的影响。摘要：Lef1和Tcf3的耗尽表明ESCs可以不受分化提示的影响，以维持ESCs的基态。
ABSTRACT Mouse and rat embryonic stem cell (ESC) self-renewal can be maintained by dual inhibition of glycogen synthase kinase 3 (GSK3) and mitogen-activated protein kinase kinase (MEK). Inhibition of GSK3 promotes ESC self-renewal by abrogating T-cell factor 3 (TCF3)-mediated repression of the pluripotency network. How inhibition of MEK mediates ESC self-renewal, however, remains largely unknown. Here, we show that inhibition of MEK can significantly suppress lymphoid enhancer factor 1 (LEF1) expression in mouse ESCs. Knockdown or knockout of Lef1 partially mimics the self-renewal-promoting effect of MEK inhibitors. Moreover, depletion of both Tcf3 and Lef1 enables maintenance of undifferentiated mouse ESCs without exogenous factors, cytokines or inhibitors. Transcriptome resequencing analysis reveals that LEF1 is closely associated with endoderm specification in ESCs. Thus, our study adds support to the notion that the key to maintaining the ESC ground state is to shield ESCs from differentiative cues. Summary: Depletion of Lef1 and Tcf3 shows that ESCs could be shielded from differentiative cues to maintain the ESC ground state.
影响因子：
4.3
作者：
Capo-Chichi CD;Smedberg JL;Rula M;Nicolas E;Yeung AT;Adamo RF;Frolov A;Godwin AK;Xu XX
通讯作者：
Xu XX