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Distinct profiles of human embryonic stem cell metabolism and mitochondria identified by oxygen

Citation

Lees, JG and Rathjen, J and Sheedy, JR and Gardner, DK and Harvey, AJ, Distinct profiles of human embryonic stem cell metabolism and mitochondria identified by oxygen, Reproduction, 150, (4) pp. 367-382. ISSN 1470-1626 (2015) [Refereed Article]

Copyright Statement

Copyright 2015 Society for Reproduction and Fertility

DOI: doi:10.1530/REP-14-0633

Abstract

Oxygen is a powerful regulator of cell function and embryonic development. It has previously been determined that oxygen regulates human embryonic stem (hES) cell glycolytic and amino acid metabolism, but the effects on mitochondria are as yet unknown. Two hES cell lines (MEL1, MEL2) were analyzed to determine the role of 5% (physiological) and 20% (atmospheric) oxygen in regulating mitochondrial activity. In response to extended physiological oxygen culture, MEL2 hES cells displayed reduced mtDNA content, mitochondrial mass and expression of metabolic genes TFAM, NRF1, PPARa and MT-ND4. Furthermore, MEL2 hES cell glucose consumption, lactate production and amino acid turnover were elevated under physiological oxygen. In stark contrast, MEL1 hES cell amino acid and carbohydrate use and mitochondrial function were relatively unaltered in response to oxygen. Furthermore, differentiation kinetics were delayed in the MEL1 hES cell line following BMP4 treatment. Here we report the first incidence of metabolic dysfunction in a hES cell population, defined as a failure to respond to oxygen concentration through the modulation of metabolism, demonstrating that hES cells can be perturbed during culture despite exhibiting the defining characteristics of pluripotent cells. Collectively, these data reveal a central role for oxygen in the regulation of hES cell metabolism and mitochondrial function, whereby physiological oxygen promotes glucose flux and suppresses mitochondrial biogenesis and gene expression.

Item Details

Item Type:Refereed Article
Research Division:Biological Sciences
Research Group:Biochemistry and Cell Biology
Research Field:Cell Development, Proliferation and Death
Objective Division:Expanding Knowledge
Objective Group:Expanding Knowledge
Objective Field:Expanding Knowledge in the Biological Sciences
Author:Rathjen, J (Dr Joy Rathjen)
ID Code:101901
Year Published:2015
Web of Science® Times Cited:6
Deposited By:Menzies Institute for Medical Research
Deposited On:2015-07-16
Last Modified:2017-11-07
Downloads:0

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