REST-miR-21-SOX2 axis maintains pluripotency in E14Tg2a.4 embryonic stem cells.
REST-miR-21-SOX2 axis maintains pluripotency in E14Tg2a.4 embryonic stem cells.
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DOI:
10.1016/j.scr.2015.05.003
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发表时间:
2015-09
影响因子:
1.2
通讯作者:
Majumder S
中科院分区:
文献类型:
--
作者:
Singh SK;Marisetty A;Sathyan P;Kagalwala M;Zhao Z;Majumder S
Our previous studies have shown that the regulatory network that maintains pluripotency in mouse embryonic stem cells (mESCs) is regulated in a context-dependent manner and can be modulated, at least in part, by re-calibration of an intracellular network of pluripotency factors as well as cues arising from the extracellular matrix. The transcriptional repressor REST represses miR-21 and, thus, regulates self-renewal in E14Tg2a.4 mESCs cultured in the absence of mouse embryonic fibroblast feeder cell effects. However, how miR-21 connects to the nuclear regulatory network has not been clear. Here, we show that miR-21, a direct target of REST-mediated repression, directly targets Sox2. Exogenously added miR-21 to mESCs decreases the expression of Sox2, decreasing mESC self-renewal, and this effect of miR-21 on mESC self-renewal can be blocked by expression of exogenous Sox2. Conversely, destabilization of Sox2 by miR-21 can be blocked by anti-miR-21. Thus, the REST-miR-21-Sox2 axis connects REST to the core nuclear pluripotency regulators in E14Tg2a.4 mESCs cultured in the absence of feeder cells.