P72. Mesenchymal progenitors distinct from muscle satellite cells contribute to ectopic fat cell formation in skeletal muscle

Abstract

Adult skeletal muscle possesses a remarkable regenerative ability. This depends on satellite cells that function as adult muscle stem cells. Despite such a high regenerative capacity, ectopic fat cells emerge in skeletal muscle in several pathological conditions. Since occurrence of ectopic fat is usually associated with loss or extreme atrophy of muscle, the idea that dysregulation of fate-switch between muscle and adipose lineages in satellite cells may underlie this pathological change has been emerged. However, the contribution of satellite cells to in vivo fat formation has not been demonstrated. Here, we prospectively identified PDGFRa + mesenchymal progenitors, distinct from satellite cells, in the mouse muscle interstitium. We show that, of the muscle-derived cell populations, only PDGFRa + cells exhibit efficient adipogenic differentiation both in vitro and in vivo. Reciprocal transplantations between regenerating and degenerating muscles, and co-culture experiments reveal that adipogenesis of PDGFRa + cells is strongly inhibited by the presence of satellite cell-derived myofibers. PDGFRa + mesenchymal progenitors can be isolated from human muscle, and adipogenic potential is highly enriched in this population. Taken together, our results suggest that PDGFRa + mesenchymal progenitors are the major contributor to ectopic fat cell formation in skeletal muscle, and emphasize that cellular interaction between muscle cells and PDGFRa + mesenchymal progenitors, not the fate decision of satellite cells, has a considerable impact on muscle homeostasis.