膜張力可調控多能幹細胞命運
作者：
小柯機器人發布時間：2020/11/20 15:03:31
英國劍橋大學Kevin J. Chalut、倫敦大學學院Ewa K. Paluch等研究人員合作發現，膜張力參與ERK介導的多能細胞命運調節。相關論文於2020年11月20日在線發表在《細胞—幹細胞》雜誌上。
為了探究形狀、力學和細胞命運之間的相互作用，研究人員使用了小鼠胚胎幹細胞（ESC），它們在進行早期分化時會改變形狀。研究人員發現形狀的變化是由β-連環蛋白介導的RhoA活性下降以及隨後質膜張力下降調節的。
值得注意的是，防止膜張力的降低會導致ESC和類胚體的早期分化缺陷。膜張力的降低促進了FGF信號成分的內吞作用，從而激活ERK信號並指導從ESC狀態退出。增加Rab5a促進的內吞作用可挽救有缺陷的早期分化。
因此，研究人員表明內吞作用的機械觸發增加調節早期分化。這些發現對於理解細胞力學如何調控生化信號以及調控細胞命運至關重要。
研究人員介紹，細胞命運的轉變通常伴隨著細胞形狀和力學的變化。然而，人們對細胞力學如何影響控制細胞命運的指導性信號的了解卻很少。
附：英文原文
Title: Membrane Tension Gates ERK-Mediated Regulation of Pluripotent Cell Fate
Author: Henry De Belly, Aki Stubb, Ayaka Yanagida, Céline Labouesse, Philip H. Jones, Ewa K. Paluch, Kevin J. Chalut
Issue&Volume: 2020-11-19
Abstract: 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.
DOI: 10.1016/j.stem.2020.10.018
Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30534-8