FOXO1-mediated lipid metabolism maintains mammalian embryos in dormancy

van der Weijden, Vera A.; Stötzel, Maximilian; Iyer, Dhanur P.; Fauler, Beatrix; Gralinska, Elzbieta; Shahraz, Mohammed; Meierhofer, David; Vingron, Martin; Rulands, Steffen; Alexandrov, Theodore; Mielke, Thorsten; Bulut-Karslioglu, Aydan

doi:10.1038/s41556-023-01325-3

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FOXO1-mediated lipid metabolism maintains mammalian embryos in dormancy

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van der Weijden, Vera A.
Stem Cell Chromatin (Aydan Bulut-Karslioglu), Dept. of Genome Regulation, (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Stötzel, Maximilian
Stem Cell Chromatin (Aydan Bulut-Karslioglu), Dept. of Genome Regulation, (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Iyer, Dhanur P.
Stem Cell Chromatin (Aydan Bulut-Karslioglu), Dept. of Genome Regulation, (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Fauler, Beatrix
Microscopy and Cryo-Electron Microscopy (Head: Thorsten Mielke), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Gralinska, Elzbieta
Transcriptional Regulation (Martin Vingron), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Meierhofer, David
Mass Spectrometry Facility (Head: David Meierhofer), Scientific Service (Head: Claudia Thurow), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Vingron, Martin
Transcriptional Regulation (Martin Vingron), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Mielke, Thorsten
Microscopy and Cryo-Electron Microscopy (Head: Thorsten Mielke), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Bulut-Karslioglu, Aydan
Stem Cell Chromatin (Aydan Bulut-Karslioglu), Dept. of Genome Regulation, (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Citation

van der Weijden, V. A., Stötzel, M., Iyer, D. P., Fauler, B., Gralinska, E., Shahraz, M., et al. (2024). FOXO1-mediated lipid metabolism maintains mammalian embryos in dormancy. Nature Cell Biology, 26(2), 181-193. doi:10.1038/s41556-023-01325-3.

Cite as: https://hdl.handle.net/21.11116/0000-000E-2C75-E

Abstract

Mammalian developmental timing is adjustable in vivo by preserving pre-implantation embryos in a dormant state called diapause. Inhibition of the growth regulator mTOR (mTORi) pauses mouse development in vitro, yet how embryonic dormancy is maintained is not known. Here we show that mouse embryos in diapause are sustained by using lipids as primary energy source. In vitro, supplementation of embryos with the metabolite L-carnitine balances lipid consumption, puts the embryos in deeper dormancy and boosts embryo longevity. We identify FOXO1 as an essential regulator of the energy balance in dormant embryos and propose, through meta-analyses of dormant cell signatures, that it may be a common regulator of dormancy across adult tissues. Our results lift a constraint on in vitro embryo survival and suggest that lipid metabolism may be a critical metabolic transition relevant for longevity and stem cell function across tissues.