FOXO1-mediated lipid metabolism maintains mammalian embryos in dormancy

作者：Vera A. van der Weijden, Maximilian Stötzel, Dhanur P. Iyer, Beatrix Fauler, Elzbieta Gralinska, Mohammed Shahraz, David Meierhofer, Martin Vingron, Steffen Rulands, Theodore Alexandrov, Thorsten Mielke, Aydan Bulut-Karslıoğlu · 发表于：Nature Cell Biology · 年份：2024 · DOI：10.1038/s41556-023-01325-3 · 被引用次数：44 · 研究领域：Genetics, Aging, and Longevity in Model Organisms、Birth, Development, and Health、Adipose Tissue and Metabolism

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.