Citation:
A. Moussaieff, Rouleau, M. , Kitsberg, D. , Cohen, M. , Levy, G. , Barasch, D. , Nemirovski, A. , Shen-Orr, S. , Laevsky, I. , Amit, M. , Bomze, D. , Elena-Herrmann, B. , Scherf, T. , Nissim-Rafinia, M. , Kempa, S. , Itskovitz-Eldor, J. , Meshorer, E. , Aberdam, D. , and Nahmias, Y. . 2015.
“Glycolysis-Mediated Changes In Acetyl-Coa And Histone Acetylation Control The Early Differentiation Of Embryonic Stem Cells”. Cell Metabolism, 21, Pp. 392-402. doi:10.1016/j.cmet.2015.02.002.
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. © 2015 Elsevier Inc.Notes:
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