Item Type: | Article |
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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 |
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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