Open Accessp107 Determines a Metabolic Checkpoint Required for Adipocyte Lineage Fates
Author(s) -
Porras Deanna P.,
Abbaszadeh Maryam,
Bhattacharya Debasmita,
D'Souza Ninoschka C.,
Edjiu Nareh R.,
Perry Christopher G. R.,
Scimè Anthony
Publication year - 2017
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2576
Subject(s) - biology , progenitor cell , microbiology and biotechnology , embryonic stem cell , reprogramming , cell fate determination , progenitor , stem cell , mitochondrion , cellular differentiation , glycolysis , cell , genetics , biochemistry , metabolism , transcription factor , gene
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. S tem C ells 2017;35:1378–1391