Membrane Tension Gates ERK-Mediated Regulation of Pluripotent Cell Fate.
Membrane Tension Gates ERK-Mediated Regulation of Pluripotent Cell Fate.
复制标题
膜张力门控ERK介导的多能细胞命运的调节。
DOI：
10.1016/j.stem.2020.10.018
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发表时间：
2021-02-04
期刊：
影响因子：
23.9
通讯作者：
Chalut KJ
中科院分区：
文献类型：
--
作者：
De Belly H;Stubb A;Yanagida A;Labouesse C;Jones PH;Paluch EK;Chalut KJ
细胞命运转变常常伴随着细胞形状和力学的变化。然而，人们对细胞力学如何影响控制细胞命运的指导信号通路知之甚少。为了探究形状、力学和命运之间的相互作用，我们使用了小鼠胚胎干细胞（ESC），它们在经历早期分化时会改变形状。我们发现形状变化是通过 β-catenin 介导的 RhoA 活性降低以及随后质膜张力的降低来调节的。引人注目的是，阻止膜张力降低会导致 ESC 和类原肠胚的早期分化缺陷。膜张力降低有利于 FGF 信号成分的内吞作用，从而激活 ERK 信号并指导退出 ESC 状态。增加 Rab5a 促进的内吞作用可挽救有缺陷的早期分化。因此，我们表明机械触发的内吞作用增加调节早期分化。我们的发现对于理解细胞力学如何调节生化信号进而调节细胞命运至关重要。胚胎干细胞早期分化过程中膜张力下降 膜张力下降导致内吞 ERK 信号传导和命运转变增加 调节轴（包括 β-catenin、RhoA 和 ERM）引发膜张力下降 防止膜张力下降导致发育缺陷 在这项研究中，Chalut 及其同事研究了细胞表面力学的变化如何驱动胚胎干细胞的早期分化和 表明阻止这种变化会导致发育缺陷。他们认为膜张力门控内吞作用的增加是调节 ERK 调节的细胞命运转变的关键机制。
Cell fate transitions are frequently accompanied by changes in cell shape and mechanics. However, how cellular mechanics affects the instructive signaling pathways controlling cell fate is poorly understood. To probe the interplay between shape, mechanics, and fate, we use mouse embryonic stem cells (ESCs), which change shape as they undergo early differentiation. We find that shape change is regulated by a β-catenin-mediated decrease in RhoA activity and subsequent decrease in the plasma membrane tension. Strikingly, preventing a decrease in membrane tension results in early differentiation defects in ESCs and gastruloids. Decreased membrane tension facilitates the endocytosis of FGF signaling components, which activate ERK signaling and direct the exit from the ESC state. Increasing Rab5a-facilitated endocytosis rescues defective early differentiation. Thus, we show that a mechanically triggered increase in endocytosis regulates early differentiation. Our findings are of fundamental importance for understanding how cell mechanics regulates biochemical signaling and therefore cell fate. Membrane tension decreases in early differentiation of embryonic stem cells Membrane tension drop leads to increase in endocytic ERK signaling and fate transition Membrane tension drop initiated by regulatory axis, including β-catenin, RhoA, and ERM Preventing membrane tension drop results in developmental defects In this study, Chalut and colleagues investigate how changes in cell surface mechanics drive early differentiation in embryonic stem cells and show that preventing this change leads to developmental defects. They identify a membrane tension gated increase in endocytosis as a key mechanism regulating an ERK-regulated cell fate transition.
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影响因子：
19
作者：
Diz-Muñoz A;Fletcher DA;Weiner OD
通讯作者：
Weiner OD
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
64.8
作者：
Gudipaty SA;Lindblom J;Loftus PD;Redd MJ;Edes K;Davey CF;Krishnegowda V;Rosenblatt J
通讯作者：
Rosenblatt J
影响因子：
4.6
作者：
Rouven Brückner B;Pietuch A;Nehls S;Rother J;Janshoff A
通讯作者：
Janshoff A
DOI：
10.1101/sqb.1995.060.01.060
发表时间：
1995-01-01
期刊：
COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY
影响因子：
--
作者：
Dai, J;Sheetz, MP
通讯作者：
Sheetz, MP