Linking substrate and nucleus via actin cytoskeleton in pluripotency maintenance of mouse embryonic stem cells
Linking substrate and nucleus via actin cytoskeleton in pluripotency maintenance of mouse embryonic stem cells
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DOI：
10.1016/j.scr.2019.101614
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发表时间：
2019-12-01
影响因子：
1.2
通讯作者：
Watanabe, Tomonobu M.
中科院分区：
文献类型：
--
作者：
David, Brit Gracy;Fujita, Hideaki;Watanabe, Tomonobu M.
小鼠胚胎干细胞的多能性受转录因子调控网络以及细胞所感知的机械刺激的调节。一直不清楚施加于质膜的机械应变是如何在小鼠胚胎干细胞（mESCs）中传递到细胞核的。我们在此基于以下发现对机械传导机制进行了研究：在贴附于软基质的细胞中，ROCK2的下调抑制了mESCs的自发分化。在研究软基质上细胞中肌动蛋白与粘着斑和细胞连接的结合作用时，诱导分化后，连接肌动蛋白与E - 钙粘蛋白的肌动蛋白丝和α - 连环蛋白的共定位减少。此外，通过对内斯普林（Nesprins）进行显性负性分析破坏肌动蛋白 - 细胞核的机械连接有助于维持多能性基因；从而揭示出由肌动蛋白 - 内斯普林连接传递的机械应变是分化过程启动所必需的。
Pluripotency of mouse embryonic stem cells is regulated by transcription factor regulatory networks as well as mechanical stimuli sensed by the cells. It has been unclear how the mechanical strain applied to the plasma membrane is transferred to the nucleus in mouse embryonic stem cells (mESCs). We here investigated the machinery of the mechanotransduction based on the finding that spontaneous differentiation of mESCs was inhibited with the downregulation of ROCK2 in cells attached to soft substrates. On examining the effects of actin bindings to both focal adhesions and cell junctions in cells on soft substrates, co-localization of actin filaments and alpha-catenin, which links actin to E-cadherin, decreased after differentiation induction. Also, disrupting actin-nucleus mechanical link through dominant negative assay of Nesprins helps to sustain the pluripotency genes; thus, revealing that mechanical strain relayed by actin-Nesprin connection is required for the initiation of the differentiation process.