title: Distinct Metabolic States Can Support Self-Renewal and Lipogenesis in Human Pluripotent Stem Cells under Different Culture Conditions.
abstract: 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 (13)C/(2)H 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.
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, CA 92037, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, CA 92037, USA.
authors.forename: Mehmet G
authors.initials: MG
authors.lastname: Badur
authors.affiliation: Department of Pharmacology, University of California, San Diego, La Jolla, CA 92037, USA.
authors.forename: Ajit S
authors.initials: AS
authors.lastname: Divakaruni
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, CA 92037, USA.
authors.forename: Seth J
authors.initials: SJ
authors.lastname: Parker
authors.affiliation: Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Belvaux, 4367 Luxembourg.
authors.forename: Christian
authors.initials: C
authors.lastname: Jäger
authors.affiliation: Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Belvaux, 4367 Luxembourg.
authors.forename: Karsten
authors.initials: K
authors.lastname: Hiller
authors.affiliation: Department of Pharmacology, University of California, San Diego, La Jolla, CA 92037, USA.
authors.forename: Anne N
authors.initials: AN
authors.lastname: Murphy
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, CA 92037, USA; Moores Cancer Center, University of California, San Diego, La Jolla, CA 92037, USA. Electronic address: cmetallo@ucsd.edu.
authors.forename: Christian M
authors.initials: CM
authors.lastname: Metallo
mesh_terms: D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D049109:Cell Proliferation / Q000502:physiology*; D000066673:Cell Self Renewal; D006801:Humans; D050155:Lipogenesis / Q000502:physiology*; D053858:Metabolic Networks and Pathways / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology*