期刊
STEM CELL REPORTS
卷 12, 期 4, 页码 728-742出版社
CELL PRESS
DOI: 10.1016/j.stemcr.2019.02.005
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资金
- Faculty of Medicine, University of Southampton
- UK Medical Research Council [G0701153]
- MRC [G0701153] Funding Source: UKRI
Glycolysis and hypoxia are key regulators of human embryonic stem cell (hESC) self-renewal, but how changes in metabolism affect gene expression is poorly understood. C-terminal binding proteins (CTBPs) are glycolytic sensors that through NADH binding link the metabolic state of the cell to its gene expression, by acting as transcriptional corepressors, or coactivators. However, the role of CTBPs in hESCs has not previously been investigated. A direct interaction between hypoxia-inducible factor 2 alpha, (HIF-2 alpha) and the CTBP proximal promoters in hESCs cultured only under hypoxia was demonstrated. Decreasing the rate of flux through glycolysis in hESCs maintained under hypoxia resulted in a reduction of CTBPs, OCT4, SOX2, and NANOG, but also in the expression of HIF-2 alpha. Silencing CTBP expression resulted in the loss of pluripotency marker expression demonstrating that CTBPs are involved in hESC maintenance. These data suggest that under hypoxia, glycolysis regulates self-renewal through HIF-2 alpha, and the induction of the metabolic sensors CTBPs.
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