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Canat, A. ; Atilla, D. ; Torres-Padilla, M.E.

Hyperosmotic stress induces 2-cell-like cells through ROS and ATR signaling.

EMBO Rep. 24:e56194 (2023)
DOI PMC
Creative Commons Lizenzvertrag
Open Access Green as soon as Postprint is submitted to ZB.
Mouse embryonic stem cells (ESCs) display pluripotency features characteristic of the inner cell mass of the blastocyst. Mouse embryonic stem cell cultures are highly heterogeneous and include a rare population of cells, which recapitulate characteristics of the 2-cell embryo, referred to as 2-cell-like cells (2CLCs). Whether and how ESC and 2CLC respond to environmental cues has not been fully elucidated. Here, we investigate the impact of mechanical stress on the reprogramming of ESC to 2CLC. We show that hyperosmotic stress induces 2CLC and that this induction can occur even after a recovery time from hyperosmotic stress, suggesting a memory response. Hyperosmotic stress in ESCs leads to accumulation of reactive-oxygen species (ROS) and ATR checkpoint activation. Importantly, preventing either elevated ROS levels or ATR activation impairs hyperosmotic-mediated 2CLC induction. We further show that ROS generation and the ATR checkpoint act within the same molecular pathway in response to hyperosmotic stress to induce 2CLCs. Altogether, these results shed light on the response of ESC to mechanical stress and on our understanding of 2CLC reprogramming.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords 2-cell-like Cells ; Hyperosmotic Stress ; Pluripotency ; Reprogramming ; Totipotency; Embryonic-like Cells; Activation; Checkpoint; Genome; Stage
ISSN (print) / ISBN 1469-221X
e-ISSN 1469-3178
Journal EMBO Reports
Quellenangaben Volume: 24, Issue: 9, Pages: , Article Number: e56194 Supplement: ,
Publisher EMBO Press
Publishing Place 111 River St, Hoboken 07030-5774, Nj Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epigenetics and Stem Cells (IES)
Grants Projekt DEAL
German Research Foundation (DFG)
Helmholtz Association