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Mechano-osmotic signals control chromatin state and fate transitions in pluripotent stem cells

ABSTRACT: Acquisition of specific cell shapes and morphologies is a central component of cell fate transitions. Although the signaling circuits and gene regulatory networks regulating pluripotent stem cell differentiation have been intensely studied, how these networks are integrated in space and time with morphological transitions and mechanical deformations that occur during state transitions remains a fundamental open question. Here, we discover that stem cell fate transitions are gated by two critical signals - nuclear envelope fluctuations and osmotic stress - that emanate from growth factor signaling-controlled changes in nuclear volume and nucleoplasm viscosity/density to subsequently trigger changes in nuclear architecture and transcription. We observe that fate transitions in the early human embryo and in an in vitro model of exit from pluripotency are associated with rapid changes in nuclear volume and nuclear envelope mechanics. These changes alter nuclear mechanosensitivity and trigger changes in nucleoplasmic viscosity and nuclear condensates to prime chromatin for a cell fate transition. However, while this mechanical priming accelerates fate transitions, sustained biochemical signals are required for efficient induction of differentiation. Our findings establish a critical mechanochemical feedback mechanism that integrates nuclear mechanics, shape and volume with biochemical signaling and chromatin state to control cell fate transition dynamics.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Stem Cell

SUBMITTER: Prerana Wagle

LAB HEAD: Sara Wickstrom

PROVIDER: PXD052588 | Pride | 2025-08-11

REPOSITORIES: Pride

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			Action	DRS
	OxidationMSites.txt	Txt
	PhosphoSTYSites.txt	Txt
	Q2_ColID_610_3501_1001.raw	Raw
	Q2_ColID_610_3501_1002.raw	Raw
	Q2_ColID_610_3501_1003.raw	Raw

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