Oxygen Regulates Human Pluripotent Stem Cell Metabolic Flux
Joint Authors
Harvey, Alexandra J.
Gardner, David K.
Lees, Jarmon G.
Cliff, Timothy S.
Gammilonghi, Amanda
Ryall, James G.
Dalton, Stephen
Source
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-17, 17 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-05-19
Country of Publication
Egypt
No. of Pages
17
Abstract EN
Metabolism has been shown to alter cell fate in human pluripotent stem cells (hPSC).
However, current understanding is almost exclusively based on work performed at 20% oxygen (air), with very few studies reporting on hPSC at physiological oxygen (5%).
In this study, we integrated metabolic, transcriptomic, and epigenetic data to elucidate the impact of oxygen on hPSC.
Using 13C-glucose labeling, we show that 5% oxygen increased the intracellular levels of glycolytic intermediates, glycogen, and the antioxidant response in hPSC.
In contrast, 20% oxygen increased metabolite flux through the TCA cycle, activity of mitochondria, and ATP production.
Acetylation of H3K9 and H3K27 was elevated at 5% oxygen while H3K27 trimethylation was decreased, conforming to a more open chromatin structure.
RNA-seq analysis of 5% oxygen hPSC also indicated increases in glycolysis, lysine demethylases, and glucose-derived carbon metabolism, while increased methyltransferase and cell cycle activity was indicated at 20% oxygen.
Our findings show that oxygen drives metabolite flux and specifies carbon fate in hPSC and, although the mechanism remains to be elucidated, oxygen was shown to alter methyltransferase and demethylase activity and the global epigenetic landscape.
American Psychological Association (APA)
Lees, Jarmon G.& Cliff, Timothy S.& Gammilonghi, Amanda& Ryall, James G.& Dalton, Stephen& Gardner, David K.…[et al.]. 2019. Oxygen Regulates Human Pluripotent Stem Cell Metabolic Flux. Stem Cells International،Vol. 2019, no. 2019, pp.1-17.
https://search.emarefa.net/detail/BIM-1209671
Modern Language Association (MLA)
Lees, Jarmon G.…[et al.]. Oxygen Regulates Human Pluripotent Stem Cell Metabolic Flux. Stem Cells International No. 2019 (2019), pp.1-17.
https://search.emarefa.net/detail/BIM-1209671
American Medical Association (AMA)
Lees, Jarmon G.& Cliff, Timothy S.& Gammilonghi, Amanda& Ryall, James G.& Dalton, Stephen& Gardner, David K.…[et al.]. Oxygen Regulates Human Pluripotent Stem Cell Metabolic Flux. Stem Cells International. 2019. Vol. 2019, no. 2019, pp.1-17.
https://search.emarefa.net/detail/BIM-1209671
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1209671