The University of Southampton
University of Southampton Institutional Repository

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 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.
2213-6711
728-742
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.
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), 728-742. (doi:10.1016/j.stemcr.2019.02.005).

Record type: Article

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.

Text
Glycolysis regulates human embryonic - Version of Record
Available under License Creative Commons Attribution.
Download (3MB)

More information

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: https://eprints.soton.ac.uk/id/eprint/429425
ISSN: 2213-6711
PURE UUID: 66429225-ec86-42a1-8942-855ae1090e6c
ORCID for Jeremy P. Blaydes: ORCID iD orcid.org/0000-0001-8525-0209

Catalogue record

Date deposited: 27 Mar 2019 17:30
Last modified: 20 Jul 2019 01:06

Export record

Altmetrics

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of https://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×