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| 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., 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. |
| 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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