Mesenchymal progenitors distinct from satellite cells contribute to ectopic fat cell formation in skeletal muscle
Mesenchymal progenitors distinct from satellite cells contribute to ectopic fat cell formation in skeletal muscle
复制标题
DOI：
10.1038/ncb2014
复制
发表时间：
2010-02-01
影响因子：
21.3
通讯作者：
Tsuchida, Kunihiro
中科院分区：
文献类型：
--
作者：
Uezumi, Akiyoshi;Fukada, So-ichiro;Tsuchida, Kunihiro
骨骼肌中的异位脂肪沉积与多种疾病密切相关，然而，这些脂肪细胞的起源尚不清楚，其形成机制也不清楚。卫星细胞具有成体肌肉干细胞的功能，但被认为具有多能性。在这里，我们发现PDGFR α(+)间充质祖细胞与卫星细胞不同，位于肌肉间质。我们发现，在肌肉来源的细胞群中，只有PDGFRa+细胞在体外和体内都表现出有效的成脂分化。再生和退化肌肉之间的相互移植以及共培养实验显示，卫星细胞来源的肌纤维的存在强烈抑制了PDGFR α(+)细胞的脂肪形成。这些结果表明，PDGFR α(+)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PDGFR α +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。
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 identify PDGFR alpha(+) mesenchymal progenitors as being distinct from satellite cells and located in the muscle interstitium. We show that, of the muscle-derived cell populations, only PDGFRa+ cells show efficient adipogenic differentiation both in vitro and in vivo. Reciprocal transplantation between regenerating and degenerating muscles, and co-culture experiments revealed that adipogenesis of PDGFR alpha(+) cells is strongly inhibited by the presence of satellite cell-derived myofibres. These results suggest that PDGFR alpha(+) mesenchymal progenitors are the major contributor to ectopic fat cell formation in skeletal muscle, and emphasize that interaction between muscle cells and PDGFRa+ mesenchymal progenitors, not the fate decision of satellite cells, has a considerable impact on muscle homeostasis.