Energy Metabolism in Mesenchymal Stem Cells During Osteogenic Differentiation.
There is emerging interest in stem cell energy metabolism and its effect on differentiation. Bioenergetic changes in differentiating bone marrow mesenchymal stem cells (MSCs) are poorly understood and were the focus of our study. Using bioenergetic profiling and transcriptomics, we have established that MSCs activate the mitochondrial process of oxidative phosphorylation (OxPhos) during osteogenic differentiation, but they maintain levels of glycolysis similar to undifferentiated cells. Consistent with their glycolytic phenotype, undifferentiated MSCs have high levels of hypoxia-inducible factor 1 (HIF-1). Osteogenically induced MSCs downregulate HIF-1 and this downregulation is required for activation of OxPhos. In summary, our work provides important insights on MSC bioenergetics and proposes a HIF-based mechanism of regulation of mitochondrial OxPhos in MSCs.
1 Center for Musculoskeletal Research, University of Rochester School of Medicine and Dentistry , Rochester, New York.
Laura C
LC
Shum
1 Center for Musculoskeletal Research, University of Rochester School of Medicine and Dentistry , Rochester, New York.
Noelle S
NS
White
2 Department of Neurology, University of Rochester School of Medicine and Dentistry , Rochester, New York.
Bradley N
BN
Mills
1 Center for Musculoskeletal Research, University of Rochester School of Medicine and Dentistry , Rochester, New York.|3 Department of Pathology, University of Rochester School of Medicine and Dentistry , Rochester, New York.
Karen L de Mesy
KL
Bentley
1 Center for Musculoskeletal Research, University of Rochester School of Medicine and Dentistry , Rochester, New York.|3 Department of Pathology, University of Rochester School of Medicine and Dentistry , Rochester, New York.
Roman A
RA
Eliseev
D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D004734:Energy Metabolism / Q000502:physiology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D010012:Osteogenesis / Q000502:physiology*
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit