title: HIF1α induced switch from bivalent to exclusively glycolytic metabolism during       ESC-to-EpiSC/hESC transition.
abstract: The function of metabolic state in stemness is poorly understood. Mouse embryonic         stem cells (ESC) and epiblast stem cells (EpiSC) are at distinct pluripotent states         representing the inner cell mass (ICM) and epiblast embryos. Human embryonic stem         cells (hESC) are similar to EpiSC stage. We now show a dramatic metabolic difference         between these two stages. EpiSC/hESC are highly glycolytic, while ESC are bivalent         in their energy production, dynamically switching from glycolysis to mitochondrial         respiration on demand. Despite having a more developed and expanding mitochondrial         content, EpiSC/hESC have low mitochondrial respiratory capacity due to low         cytochrome c oxidase (COX) expression. Similarly, in vivo epiblasts         suppress COX levels. These data reveal EpiSC/hESC functional similarity to the         glycolytic phenotype in cancer (Warburg effect). We further show that         hypoxia-inducible factor 1α (HIF1α) is sufficient to drive ESC to a         glycolytic Activin/Nodal-dependent EpiSC-like stage. This metabolic switch during         early stem-cell development may be deterministic.
authors.affiliation: H Ruohola-Baker Department of Biology, University of Washington, Seattle, WA, USA.
authors.forename: Wenyu
authors.initials: W
authors.lastname: Zhou
authors.forename: Michael
authors.initials: M
authors.lastname: Choi
authors.forename: Daciana
authors.initials: D
authors.lastname: Margineantu
authors.forename: Lilyana
authors.initials: L
authors.lastname: Margaretha
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hesson
authors.forename: Christopher
authors.initials: C
authors.lastname: Cavanaugh
authors.forename: C Anthony
authors.initials: CA
authors.lastname: Blau
authors.forename: Marshall S
authors.initials: MS
authors.lastname: Horwitz
authors.forename: David
authors.initials: D
authors.lastname: Hockenbery
authors.forename: Carol
authors.initials: C
authors.lastname: Ware
authors.forename: Hannele
authors.initials: H
authors.lastname: Ruohola-Baker
mesh_terms: D028341:Activins / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D004272:DNA, Mitochondrial / Q000032:analysis; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000502:physiology*; D005260:Female; D006019:Glycolysis; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D008810:Mice, Inbred C57BL; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; C497442:HIF1A protein, human; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D028341:Activins; D000255:Adenosine Triphosphate; D011451:Prostaglandin-Endoperoxide Synthases