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

Item Type:Article
Title:Glycolysis-mediated changes in acetyl-CoA and histone acetylation control the early differentiation of embryonic stem cells
Creators Name:Moussaieff, A. and Rouleau, M. and Kitsberg, D. and Cohen, M. and Levy, G. and Barasch, D. and Nemirovski, A. and Shen-Orr, S. and Laevsky, I. and Amit, M. and Bomze, D. and Elena-Herrmann, B. and Scherf, T. and Nissim-Rafinia, M. and Kempa, S. and Itskovitz-Eldor, J. and Meshorer, E. and Aberdam, D. and Nahmias, Y.
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.
Keywords:Acetyl Coenzyme A, Acetylation, Cell Differentiation, Cell Line, Embryonic Stem Cells, Genetic Transcription, Glycolysis, Histones, Animals, Mice
Source:Cell Metabolism
ISSN:1550-4131
Publisher:Cell Press / Elsevier (U.S.A.)
Volume:21
Number:3
Page Range:392-402
Date:3 March 2015
Official Publication:https://doi.org/10.1016/j.cmet.2015.02.002
PubMed:View item in PubMed

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