英国剑桥大学Kevin J. Chalut、伦敦大学学院Ewa K. Paluch等研究人员合作发现，膜张力参与ERK介导的多能细胞命运调节。相关论文于2020年11月20日在线发表在《细胞—干细胞》杂志上。

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