Muscle injury activates resident fibro/adipogenic progenitors that facilitate myogenesis.

Efficient tissue regeneration is dependent on the coordinated responses of multiple cell types. Here, we describe a new subpopulation of fibro/adipogenic progenitors (FAPs) resident in muscle tissue but arising from a distinct developmental lineage. Transplantation of purified FAPs results in the generation of ectopic white fat when delivered subcutaneously or intramuscularly in a model of fatty infiltration, but not in healthy muscle, suggesting that the environment controls their engraftment. These cells are quiescent in intact muscle but proliferate efficiently in response to damage. FAPs do not generate myofibres, but enhance the rate of differentiation of primary myogenic progenitors in co-cultivation experiments. In summary, FAPs expand upon damage to provide a transient source of pro-differentiation signals for proliferating myogenic progenitors.

Depot-specific differences in adipogenic progenitor abundance and proliferative response to high-fat diet.

White adipose tissue (fat) is the primary organ for energy storage and its regulation has serious implications on human health. Excess fat tissue causes significant morbidity, and adipose tissue dysfunction caused by excessive adipocyte hypertrophy has been proposed to play a significant role in the pathogenesis of metabolic disease. Studies in both humans and animal models show that metabolic dysfunction is more closely associated with visceral than subcutaneous fat accumulation. Here, we show that in mice fed a high-fat diet, visceral fat (VAT) grows mostly by hypertrophy and subcutaneous fat (SAT) by hyperplasia, providing a rationale for the different effects of specific adipose depots on metabolic health. To address whether depot expansion is controlled at the level of stem/progenitor cells, we developed a strategy to prospectively identify adipogenic progenitors (APs) from both depots. Clonogenic assays and in vivo bromodeoxyuridine (BrdU) studies show that APs are eightfold more abundant in SAT than VAT, and that AP proliferation is significantly increased in SAT but not VAT in response to high-fat diet. Our results suggest that depot-specific differences in AP abundance and proliferation underlie whether a fat depot expands by hypertrophy or hyperplasia, and thus may have important implications on the development of metabolic disease. In addition, we provide the first evidence that dietary inputs can modulate the proliferation of adipogenic progenitors in adults.