title: p107 Determines a Metabolic Checkpoint Required for Adipocyte Lineage Fates.
abstract: We show that the transcriptional corepressor p107 orchestrates a metabolic checkpoint that determines adipocyte lineage fates for non-committed progenitors. p107 accomplishes this when stem cell commitment would normally occur in growth arrested cells. p107-deficient embryonic progenitors are characterized by a metabolic state resembling aerobic glycolysis that is necessary for their pro-thermogenic fate. Indeed, during growth arrest they have a reduced capacity for NADH partitioning between the cytoplasm and mitochondria. Intriguingly, this occurred despite an increase in the capacity for mitochondrial oxidation of non-glucose substrates. The significance of metabolic reprogramming is underscored by the disruption of glycolytic capacities in p107-depleted progenitors that reverted their fates from pro-thermogenic to white adipocytes. Moreover, the manipulation of glycolytic capacity on nonspecified embryonic and adult progenitors forced their beige fat commitment. These innovative findings introduce a new approach to increase pro-thermogenic adipocytes based on simply promoting aerobic glycolysis to manipulate nonspecified progenitor fate decisions. Stem Cells 2017;35:1378-1391.
authors.affiliation: Stem Cell Research Group, York University, Toronto, Ontario, Canada.|Molecular, Cellular and Integrative Physiology, Faculty of Health, York University, Toronto, Ontario, Canada.
authors.forename: Deanna P
authors.initials: DP
authors.lastname: Porras
authors.affiliation: Stem Cell Research Group, York University, Toronto, Ontario, Canada.|Molecular, Cellular and Integrative Physiology, Faculty of Health, York University, Toronto, Ontario, Canada.
authors.forename: Maryam
authors.initials: M
authors.lastname: Abbaszadeh
authors.affiliation: Stem Cell Research Group, York University, Toronto, Ontario, Canada.|Molecular, Cellular and Integrative Physiology, Faculty of Health, York University, Toronto, Ontario, Canada.
authors.forename: Debasmita
authors.initials: D
authors.lastname: Bhattacharya
authors.affiliation: Stem Cell Research Group, York University, Toronto, Ontario, Canada.|Molecular, Cellular and Integrative Physiology, Faculty of Health, York University, Toronto, Ontario, Canada.
authors.forename: Ninoschka C
authors.initials: NC
authors.lastname: D'Souza
authors.affiliation: Stem Cell Research Group, York University, Toronto, Ontario, Canada.|Molecular, Cellular and Integrative Physiology, Faculty of Health, York University, Toronto, Ontario, Canada.
authors.forename: Nareh R
authors.initials: NR
authors.lastname: Edjiu
authors.affiliation: Molecular, Cellular and Integrative Physiology, Faculty of Health, York University, Toronto, Ontario, Canada.
authors.forename: Christopher G R
authors.initials: CGR
authors.lastname: Perry
authors.affiliation: Stem Cell Research Group, York University, Toronto, Ontario, Canada.|Molecular, Cellular and Integrative Physiology, Faculty of Health, York University, Toronto, Ontario, Canada.
authors.forename: Anthony
authors.initials: A
authors.lastname: Scimè
mesh_terms: D052437:Adipocytes, Brown / Q000166:cytology*; D052438:Adipocytes, White / Q000166:cytology*; D000332:Aerobiosis; D000818:Animals; D059447:Cell Cycle Checkpoints; D002460:Cell Line; D019070:Cell Lineage; D002467:Cell Nucleus / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology; D055785:Gene Knockdown Techniques; D006019:Glycolysis; D018345:Mice, Knockout; D008954:Models, Biological; D010084:Oxidation-Reduction; D050720:Retinoblastoma-Like Protein p107 / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D050720:Retinoblastoma-Like Protein p107
keywords: Aerobic glycolysis; Beige/brown adipocytes; Metabolism; Progenitor fate; p107