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Membrane Tension Gates ERK-Mediated Regulation of Pluripotent Cell Fate

De Belly, H; Stubb, A; Yanagida, A; Labouesse, C; Jones, PH; Paluch, EK; Chalut, KJ; (2020) Membrane Tension Gates ERK-Mediated Regulation of Pluripotent Cell Fate. Cell Stem Cell 10.1016/j.stem.2020.10.018. (In press). Green open access

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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 b-cateninmediated 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.

Type: Article
Title: Membrane Tension Gates ERK-Mediated Regulation of Pluripotent Cell Fate
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.stem.2020.10.018
Publisher version: https://doi.org/10.1016/j.stem.2020.10.018
Language: English
Additional information: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Beta-catenin, Cell fate choice, Cell surface mechanics, ERK, Embryonic stem cells, Endocytosis, Membrane tension, mechanical signalling, pluripotency
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Physics and Astronomy
URI: https://discovery.ucl.ac.uk/id/eprint/10118686
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