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Oxygen modulates human embryonic stem cell metabolism in the absence of changes in self-renewal


Harvey, AJ and Rathjen, J and Yu, LJ and Gardner, DK, Oxygen modulates human embryonic stem cell metabolism in the absence of changes in self-renewal, Reproduction, Fertility and Development, 28, (4) pp. 446-458. ISSN 1031-3613 (2016) [Refereed Article]

Copyright Statement

Copyright 2016 CSIRO

DOI: doi:10.1071/RD14013


Human embryonic stem (ES) cells are routinely cultured under atmospheric oxygen (~20%), a concentration that is known to impair embryo development in vitro and is likely to be suboptimal for maintaining human ES cells compared with physiological (~5%) oxygen conditions. Conflicting reports exist on the effect of oxygen during human ES cell culture and studies have been largely limited to characterisation of typical stem cell markers or analysis of global expression changes. This study aimed to identify physiological markers that could be used to evaluate the metabolic impact of oxygen on the MEL-2 human ES cell line after adaptation to either 5% or 20% oxygen in extended culture. ES cells cultured under atmospheric oxygen displayed decreased glucose consumption and lactate production when compared with those cultured under 5% oxygen, indicating an overall higher flux of glucose through glycolysis under physiological conditions. Higher glucose utilisation at 5% oxygen was accompanied by significantly increased expression of all glycolytic genes analysed. Analysis of amino acid turnover highlighted differences in the consumption of glutamine and threonine and in the production of proline. The expression of pluripotency and differentiation markers was, however, unaltered by oxygen and no observable difference in proliferation between cells cultured in 5% and 20% oxygen was seen. Apoptosis was elevated under 5% oxygen conditions. Collectively these data suggest that culture conditions, including oxygen concentration, can significantly alter human ES cell physiology with coordinated changes in gene expression, in the absence of detectable alterations in undifferentiated marker expression.

Item Details

Item Type:Refereed Article
Keywords:amino acids, culture, glycolysis, microenvironment, pluripotency
Research Division:Biological Sciences
Research Group:Biochemistry and cell biology
Research Field:Cell metabolism
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in the biological sciences
UTAS Author:Rathjen, J (Dr Joy Rathjen)
ID Code:114559
Year Published:2016
Web of Science® Times Cited:20
Deposited By:Medicine
Deposited On:2017-02-17
Last Modified:2017-11-07

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