Glycolysis-mediated changes in acetyl-CoA and histone acetylation control the early differentiation of embryonic stem cells - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Cell Metabolism Année : 2015

Glycolysis-mediated changes in acetyl-CoA and histone acetylation control the early differentiation of embryonic stem cells

Daniel Kitsberg
  • Fonction : Auteur
Gahl Levy
  • Fonction : Auteur
Dinorah Barasch
  • Fonction : Auteur
Shai Shen-Orr
  • Fonction : Auteur
Ilana Laevsky
  • Fonction : Auteur
David Bomze
  • Fonction : Auteur
Tali Scherf
  • Fonction : Auteur
Malka Nissim-Rafinia
  • Fonction : Auteur
Stefan Kempa
  • Fonction : Auteur
Joseph Itskovitz-Eldor
  • Fonction : Auteur
Eran Meshorer
  • Fonction : Auteur

Résumé

Loss of pluripotency is a gradual event whose initiating factors are largely unknown. Here we report the earliest metabolic changes induced during the first hours of differentiation. High-resolution NMR identified 44 metabolites and a distinct metabolic transition occurring during early differentiation. Metabolic and transcriptional analyses showed that pluripotent cells produced acetyl-CoA through glycolysis and rapidly lost this function during differentiation. Importantly, modulation of glycolysis blocked histone deacetylation and differentiation in human and mouse embryonic stem cells. Acetate, a precursor of acetylCoA, delayed differentiation and blocked early histone deacetylation in a dose-dependent manner. Inhibitors upstream of acetyl-CoA caused differentiation of pluripotent cells, while those downstream delayed differentiation. Our results show a metabolic switch causing a loss of histone acetylation and pluripotent state during the first hours of differentiation. Our data highlight the important role metabolism plays in pluripotency and suggest that a glycolytic switch controlling histone acetylation can release stem cells from pluripotency.

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Dates et versions

hal-01256018 , version 1 (14-01-2016)

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Arieh Moussaieff, Matthieu Rouleau, Daniel Kitsberg, Merav Cohen, Gahl Levy, et al.. Glycolysis-mediated changes in acetyl-CoA and histone acetylation control the early differentiation of embryonic stem cells. Cell Metabolism, 2015, 21 (3), pp.349-350. ⟨10.1016/j.cmet.2015.02.002⟩. ⟨hal-01256018⟩
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