Glycolysis regulates human embryonic stem cell self-renewal under hypoxia through HIF-2α and the glycolytic sensors CTBPs
Glycolysis regulates human embryonic stem cell self-renewal under hypoxia through HIF-2α and the glycolytic sensors CTBPs
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 2α (HIF-2α) 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-2α. 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-2α and the induction of the metabolic sensors CTBPs.
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Arthur, Sophie A.
f34500a2-4293-413e-ac8d-5470a3c4adff
Blaydes, Jeremy P.
e957f999-fd91-4f77-ad62-5b4ef069b15b
Houghton, Franchesca D.
53946041-127e-45a8-9edb-bf4b3c23005f
9 April 2019
Arthur, Sophie A.
f34500a2-4293-413e-ac8d-5470a3c4adff
Blaydes, Jeremy P.
e957f999-fd91-4f77-ad62-5b4ef069b15b
Houghton, Franchesca D.
53946041-127e-45a8-9edb-bf4b3c23005f
Arthur, Sophie A., Blaydes, Jeremy P. and Houghton, Franchesca D.
(2019)
Glycolysis regulates human embryonic stem cell self-renewal under hypoxia through HIF-2α and the glycolytic sensors CTBPs.
Stem Cell Reports, 12 (4), .
(doi:10.1016/j.stemcr.2019.02.005).
Abstract
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 2α (HIF-2α) 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-2α. 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-2α and the induction of the metabolic sensors CTBPs.
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Glycolysis regulates human embryonic
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Accepted/In Press date: 14 February 2019
e-pub ahead of print date: 14 March 2019
Published date: 9 April 2019
Identifiers
Local EPrints ID: 429425
URI: http://eprints.soton.ac.uk/id/eprint/429425
ISSN: 2213-6711
PURE UUID: 66429225-ec86-42a1-8942-855ae1090e6c
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Date deposited: 27 Mar 2019 17:30
Last modified: 16 Mar 2024 03:49
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Author:
Sophie A. Arthur
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