Acute dietary methionine restriction triggers cell cycle arrest and reversible growth defects in the neocortex

Summary: Methionine is indispensable for cell proliferation, stem cell maintenance, and epigenetic regulation, three processes that are central to embryonic development. Here, we assessed the consequences of short-term dietary methionine restriction (MR) on mouse embryonic organ growth. In compariso...

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Main Authors: Sulov Saha, Clémence Debacq, Christophe Audouard, Thomas Jungas, Pierrick Dupré, Fawal Mohamad-Ali, Clément Chapat, Henri-Alexandre Michaud, Laurent Le Cam, Matthieu Lacroix, David Ohayon, Alice Davy
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004225009666
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Summary:Summary: Methionine is indispensable for cell proliferation, stem cell maintenance, and epigenetic regulation, three processes that are central to embryonic development. Here, we assessed the consequences of short-term dietary methionine restriction (MR) on mouse embryonic organ growth. In comparison with growth of the liver and heart which was unaffected, MR for 5 days led to a severe reduction in neuronal production and neocortex growth. Progenitor cohort labeling revealed a time-dependent sensitivity to MR and cell cycle analysis indicated that progenitors are stalled in S/G2 phases following MR. Unexpectedly, neuronal production was completely rescued at birth when switching the dam back to control diet, uncovering a mechanism of catch-up growth. We used imaging mass cytometry to probe metabolic and epigenetic markers in neural progenitors following MR and during catch-up growth. Altogether, our data uncover a reversible state of quiescence in S/G2 which is metabolically distinct from G0 quiescence and associated with efficient catch-up growth of the neocortex.
ISSN:2589-0042