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

Arieh Moussaieff*, Matthieu Rouleau, Daniel Kitsberg, Merav Cohen, Gahl Levy, Dinorah Barasch, Alina Nemirovski, Shai Shen-Orr, Ilana Laevsky, Michal Amit, David Bomze, Bénédicte Elena-Herrmann, Tali Scherf, Malka Nissim-Rafinia, Stefan Kempa, Joseph Itskovitz-Eldor, Eran Meshorer, Daniel Aberdam, Yaakov Nahmias

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

479 Scopus citations

Abstract

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 acetyl-CoA, 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.

Original languageAmerican English
Pages (from-to)392-402
Number of pages11
JournalCell Metabolism
Volume21
Issue number3
DOIs
StatePublished - 3 Mar 2015

Bibliographical note

Publisher Copyright:
© 2015 Elsevier Inc.

Fingerprint

Dive into the research topics of 'Glycolysis-mediated changes in acetyl-CoA and histone acetylation control the early differentiation of embryonic stem cells'. Together they form a unique fingerprint.

Cite this