Membrane Tension Gates ERK-Mediated Regulation of Pluripotent Cell Fate.

Cell Stem Cell
Henry De BellyKevin J Chalut

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.

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Citations

Feb 6, 2021·Cell Stem Cell·Jonathon M Muncie, Valerie M Weaver
Jun 10, 2021·Developmental Cell·Mary-Kate HaywardValerie M Weaver
Jul 30, 2021·Journal of Cell Science·Agathe ChaigneEwa K Paluch
Aug 8, 2021·Cells & Development·Lior AtiaAdrian F Pegoraro
Aug 22, 2021·Seminars in Cell & Developmental Biology·Pedro Gómez-GálvezJavier Buceta

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Datasets Mentioned

BETA
GSE159433

Methods Mentioned

BETA
optical tweezers
scanning electron microscopy
force measurements
FRET
pull-down
force measurement
transfection
RNA-seq
GTPases
transfections

Software Mentioned

GSNAP
DAVID
Prism
FastQC
DESeq2
Ensembl
Fiji
HTSeq
LifeAct
ImageJ Fiji

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