2. Academic Validation
  3. FOXO1-mediated lipid metabolism maintains mammalian embryos in dormancy

FOXO1-mediated lipid metabolism maintains mammalian embryos in dormancy

  • Nat Cell Biol. 2024 Jan 4. doi: 10.1038/s41556-023-01325-3.
Vera A van der Weijden 1,  Maximilian Stötzel 1 2,  Dhanur P Iyer 1 2,  Beatrix Fauler 3,  Elzbieta Gralinska 4 5,  Mohammed Shahraz 6,  David Meierhofer 7,  Martin Vingron 4,  Steffen Rulands 8 9,  Theodore Alexandrov 6,  Thorsten Mielke 3,  Aydan Bulut-Karslioglu 10
Affiliations

Affiliations

  • 1 Stem Cell Chromatin Group, Department of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin, Germany.
  • 2 Institute of Chemistry and Biochemistry, Department of Biology, Chemistry and Pharmacy, Freie Universität Berlin, Berlin, Germany.
  • 3 Microscopy and Cryo-Electron Microscopy Facility, Max Planck Institute for Molecular Genetics, Berlin, Germany.
  • 4 Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany.
  • 5 Roche Innovation Center Zurich, Schlieren, Switzerland.
  • 6 Structural and Computational Biology, European Molecular Biology Laboratory, Heidelberg, Germany.
  • 7 Mass Spectrometry Facility, Max Planck Institute for Molecular Genetics, Berlin, Germany.
  • 8 Max Planck Institute for the Physics of Complex Systems, Dresden, Germany.
  • 9 Arnold Sommerfeld Center for Theoretical Physics, Ludwig-Maximilians-Universität München, Munich, Germany.
  • 10 Stem Cell Chromatin Group, Department of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin, Germany. [email protected].
PMID: 38177284 DOI: 10.1038/s41556-023-01325-3
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.

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