Division for Therapies against Intractable Diseases, Institute for Comprehensive Medical Science, Fujita Health University, 1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi 470-1192, Japan.
Nat Cell Biol. 2010 Feb;12(2):143-52. doi: 10.1038/ncb2014. Epub 2010 Jan 17.
Ectopic fat deposition in skeletal muscle is closely associated with several disorders, however, the origin of these adipocytes is not clear, nor is the mechanism of their formation. Satellite cells function as adult muscle stem cells but are proposed to possess multipotency. Here, we prospectively identify PDGFRalpha(+) mesenchymal progenitors as being distinct from satellite cells and located in the muscle interstitium. We show that, of the muscle-derived cell populations, only PDGFRalpha(+) cells show efficient adipogenic differentiation both in vitro and in vivo. Reciprocal transplantations between regenerating and degenerating muscles, and co-culture experiments revealed that adipogenesis of PDGFRalpha(+) cells is strongly inhibited by the presence of satellite cell-derived myofibres. These results suggest that PDGFRalpha(+) mesenchymal progenitors are the major contributor to ectopic fat cell formation in skeletal muscle, and emphasize that interaction between muscle cells and PDGFRalpha(+) mesenchymal progenitors, not the fate decision of satellite cells, has a considerable impact on muscle homeostasis.
骨骼肌异位脂肪沉积与多种疾病密切相关，但这些脂肪细胞的来源尚不清楚，其形成机制也不明确。卫星细胞作为成体肌肉干细胞，但被认为具有多能性。在这里，我们前瞻性地确定 PDGFRalpha(+)间充质祖细胞与卫星细胞不同，位于肌肉间质中。我们表明，在肌肉来源的细胞群体中，只有 PDGFRalpha(+)细胞在体外和体内均显示出有效的成脂分化能力。在再生和退化肌肉之间的相互移植和共培养实验表明，PDGFRalpha(+)细胞的成脂分化受到卫星细胞衍生的肌纤维的强烈抑制。这些结果表明，PDGFRalpha(+)间充质祖细胞是骨骼肌异位脂肪细胞形成的主要贡献者，并强调肌肉细胞与 PDGFRalpha(+)间充质祖细胞之间的相互作用，而不是卫星细胞的命运决定，对肌肉稳态有相当大的影响。
