Oxygen modulates human embryonic stem cell metabolism in the absence of changes in self-renewal
Alexandra J. Harvey A B , Joy Rathjen A B C , Lijia Jackie Yu A D and David K. Gardner A B E
+ Author Affiliations
- Author Affiliations
A Department of Zoology, University of Melbourne, Royal Parade, Parkville, Vic. 3010, Australia.
B Stem Cells Australia, Melbourne Brain Centre, University of Melbourne, 30 Royal Parade, Parkville, Vic. 3010, Australia.
C Menzies Research Institute Tasmania, University of Tasmania, 17 Liverpool Street, Hobart, Tas. 7000, Australia.
D Present address: Cellestis International Pty Ltd, 1341 Dandenong Road, Chadstone, Vic. 3148, Australia.
E Corresponding author. Email: david.gardner@unimelb.edu.au
Reproduction, Fertility and Development 28(4) 446-458 https://doi.org/10.1071/RD14013
Submitted: 15 January 2014 Accepted: 2 July 2014 Published: 22 August 2014
Abstract
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.
Additional keywords: amino acids, culture, glycolysis, microenvironment, pluripotency.
References
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