TY - JOUR
T1 - Mesenchymal progenitors distinct from satellite cells contribute to ectopic fat cell formation in skeletal muscle
AU - Uezumi, Akiyoshi
AU - Fukada, So Ichiro
AU - Yamamoto, Naoki
AU - Takeda, Shin'Ichi
AU - Tsuchida, Kunihiro
N1 - Funding Information:
We thank S. Miura, M. Nakatani and T. Sato for technical assistance, F. Rossi for providing DyLight 649-conjugated rat anti-integrin α7, A. Miyajima for providing a rat anti-Dlk1 antibody and N. Hashimoto for providing a rabbit anti-myogenin antibody. This work was supported by JSPS KAKENHI (18890216; to A.U.), MEXT KAKENHI (21790884; to A.U.), a research grant (H20-018) on psychiatric and neurological diseases and mental health and a research grant (20B-13) for nervous and mental disorders from the Ministry of Health, Labour and Welfare.
PY - 2010/2
Y1 - 2010/2
N2 - 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 PDGFRα+ mesenchymal progenitors as being distinct from satellite cells and located in the muscle interstitium. We show that, of the muscle-derived cell populations, only PDGFRα+ 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 PDGFRα+ cells is strongly inhibited by the presence of satellite cell-derived myofibres. These results suggest that PDGFRα+ mesenchymal progenitors are the major contributor to ectopic fat cell formation in skeletal muscle, and emphasize that interaction between muscle cells and PDGFRα+ mesenchymal progenitors, not the fate decision of satellitecells, has a considerable impact on muscle homeostasis.
AB - 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 PDGFRα+ mesenchymal progenitors as being distinct from satellite cells and located in the muscle interstitium. We show that, of the muscle-derived cell populations, only PDGFRα+ 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 PDGFRα+ cells is strongly inhibited by the presence of satellite cell-derived myofibres. These results suggest that PDGFRα+ mesenchymal progenitors are the major contributor to ectopic fat cell formation in skeletal muscle, and emphasize that interaction between muscle cells and PDGFRα+ mesenchymal progenitors, not the fate decision of satellitecells, has a considerable impact on muscle homeostasis.
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U2 - 10.1038/ncb2014
DO - 10.1038/ncb2014
M3 - Article
C2 - 20081842
AN - SCOPUS:75949130333
VL - 12
SP - 143
EP - 152
JO - Nature Cell Biology
JF - Nature Cell Biology
SN - 1465-7392
IS - 2
ER -