Distinct Metabolic States Can Support Self-Renewal and Lipogenesis in Human Pluripotent Stem Cells under Different Culture Conditions
Recent studies have suggested that human pluripotent stem cells (hPSCs) depend primarily on glycolysis and only increase oxidative metabolism during differentiation. Here, we demonstrate that both glycolytic and oxidative metabolism can support hPSC growth and that the metabolic phenotype of hPSCs i...
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doaj-87aa1c1a56234be6b0eadb27c24ce8d22020-11-25T01:17:24ZengElsevierCell Reports2211-12472016-08-011661536154710.1016/j.celrep.2016.06.102Distinct Metabolic States Can Support Self-Renewal and Lipogenesis in Human Pluripotent Stem Cells under Different Culture ConditionsHui Zhang0Mehmet G. Badur1Ajit S. Divakaruni2Seth J. Parker3Christian Jäger4Karsten Hiller5Anne N. Murphy6Christian M. Metallo7Department of Bioengineering, University of California, San Diego, La Jolla, CA 92037, USADepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92037, USADepartment of Pharmacology, University of California, San Diego, La Jolla, CA 92037, USADepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92037, USALuxembourg Centre for Systems Biomedicine, University of Luxembourg, Belvaux, 4367 LuxembourgLuxembourg Centre for Systems Biomedicine, University of Luxembourg, Belvaux, 4367 LuxembourgDepartment of Pharmacology, University of California, San Diego, La Jolla, CA 92037, USADepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92037, USARecent studies have suggested that human pluripotent stem cells (hPSCs) depend primarily on glycolysis and only increase oxidative metabolism during differentiation. Here, we demonstrate that both glycolytic and oxidative metabolism can support hPSC growth and that the metabolic phenotype of hPSCs is largely driven by nutrient availability. We comprehensively characterized hPSC metabolism by using 13C/2H stable isotope tracing and flux analysis to define the metabolic pathways supporting hPSC bioenergetics and biosynthesis. Although glycolytic flux consistently supported hPSC growth, chemically defined media strongly influenced the state of mitochondrial respiration and fatty acid metabolism. Lipid deficiency dramatically reprogramed pathways associated with fatty acid biosynthesis and NADPH regeneration, altering the mitochondrial function of cells and driving flux through the oxidative pentose phosphate pathway. Lipid supplementation mitigates this metabolic reprogramming and increases oxidative metabolism. These results demonstrate that self-renewing hPSCs can present distinct metabolic states and highlight the importance of medium nutrients on mitochondrial function and development.http://www.sciencedirect.com/science/article/pii/S2211124716308713 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hui Zhang Mehmet G. Badur Ajit S. Divakaruni Seth J. Parker Christian Jäger Karsten Hiller Anne N. Murphy Christian M. Metallo |
spellingShingle |
Hui Zhang Mehmet G. Badur Ajit S. Divakaruni Seth J. Parker Christian Jäger Karsten Hiller Anne N. Murphy Christian M. Metallo Distinct Metabolic States Can Support Self-Renewal and Lipogenesis in Human Pluripotent Stem Cells under Different Culture Conditions Cell Reports |
author_facet |
Hui Zhang Mehmet G. Badur Ajit S. Divakaruni Seth J. Parker Christian Jäger Karsten Hiller Anne N. Murphy Christian M. Metallo |
author_sort |
Hui Zhang |
title |
Distinct Metabolic States Can Support Self-Renewal and Lipogenesis in Human Pluripotent Stem Cells under Different Culture Conditions |
title_short |
Distinct Metabolic States Can Support Self-Renewal and Lipogenesis in Human Pluripotent Stem Cells under Different Culture Conditions |
title_full |
Distinct Metabolic States Can Support Self-Renewal and Lipogenesis in Human Pluripotent Stem Cells under Different Culture Conditions |
title_fullStr |
Distinct Metabolic States Can Support Self-Renewal and Lipogenesis in Human Pluripotent Stem Cells under Different Culture Conditions |
title_full_unstemmed |
Distinct Metabolic States Can Support Self-Renewal and Lipogenesis in Human Pluripotent Stem Cells under Different Culture Conditions |
title_sort |
distinct metabolic states can support self-renewal and lipogenesis in human pluripotent stem cells under different culture conditions |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2016-08-01 |
description |
Recent studies have suggested that human pluripotent stem cells (hPSCs) depend primarily on glycolysis and only increase oxidative metabolism during differentiation. Here, we demonstrate that both glycolytic and oxidative metabolism can support hPSC growth and that the metabolic phenotype of hPSCs is largely driven by nutrient availability. We comprehensively characterized hPSC metabolism by using 13C/2H stable isotope tracing and flux analysis to define the metabolic pathways supporting hPSC bioenergetics and biosynthesis. Although glycolytic flux consistently supported hPSC growth, chemically defined media strongly influenced the state of mitochondrial respiration and fatty acid metabolism. Lipid deficiency dramatically reprogramed pathways associated with fatty acid biosynthesis and NADPH regeneration, altering the mitochondrial function of cells and driving flux through the oxidative pentose phosphate pathway. Lipid supplementation mitigates this metabolic reprogramming and increases oxidative metabolism. These results demonstrate that self-renewing hPSCs can present distinct metabolic states and highlight the importance of medium nutrients on mitochondrial function and development. |
url |
http://www.sciencedirect.com/science/article/pii/S2211124716308713 |
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