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Thermogenic (beige and brown) adipocytes protect animals against obesity and metabolic disease. However, little is known about the mechanisms that commit stem cells toward different adipocyte lineages. We show here that p107 is a master regulator of adipocyte lineage fates, its suppression required for commitment of stem cells to the brown‐type fate. p107 is strictly expressed in the stem cell compartment of white adipose tissue depots and completely absent in brown adipose tissue. Remarkably, p107‐deficient stem cells uniformly give rise to brown‐type adipocytes in vitro and in vivo. Furthermore, brown fat programming of mesenchymal stem cells by PRDM‐BF1‐RIZ1 homologous domain containing 16 (Prdm16) was associated with a dramatic reduction of p107 levels. Indeed, Prdm16 directly suppressed p107 transcription via promoter binding. Notably, the sustained expression of p107 blocked the ability of Prdm16 to induce brown fat genes. These findings demonstrate that p107 expression in stem cells commits cells to the white versus brown adipose lineage. S tem  C ells   2014;32:1323–1336

p107 Is a Crucial Regulator for Determining the Adipocyte Lineage Fate Choices of Stem Cells