Hyperosmotic stress induces 2-cell-like cells through ROS and ATR signaling.
EMBO Rep. 24:e56194 (2023)
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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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
2-cell-like Cells ; Hyperosmotic Stress ; Pluripotency ; Reprogramming ; Totipotency; Embryonic-like Cells; Activation; Checkpoint; Genome; Stage
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2023
Prepublished im Jahr
0
HGF-Berichtsjahr
2023
ISSN (print) / ISBN
1469-221X
e-ISSN
1469-3178
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 24,
Heft: 9,
Seiten: ,
Artikelnummer: e56194
Supplement: ,
Reihe
Verlag
EMBO Press
Verlagsort
111 River St, Hoboken 07030-5774, Nj Usa
Tag d. mündl. Prüfung
0000-00-00
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Prüfer
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Veröffentlichungsdatum
0000-00-00
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0000-00-00
Anmelder/Inhaber
weitere Inhaber
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Priorität
Begutachtungsstatus
Peer reviewed
POF Topic(s)
30204 - Cell Programming and Repair
Forschungsfeld(er)
Stem Cell and Neuroscience
PSP-Element(e)
G-506200-001
Förderungen
Projekt DEAL
German Research Foundation (DFG)
Helmholtz Association
Copyright
Erfassungsdatum
2023-10-06