Functional heterogeneity of side population cells in skeletal muscle.
Skeletal muscle regeneration has been exclusively attributed to myogenic precursors, satellite cells. A stem cell-rich fraction referred to as side population (SP) cells also resides in skeletal muscle, but its roles in muscle regeneration remain unclear. We found that muscle SP cells could be subdivided into three sub-fractions using CD31 and CD45 markers. The majority of SP cells in normal non-regenerating muscle expressed CD31 and had endothelial characteristics. However, CD31(-)CD45(-) SP cells, which are a minor subpopulation in normal muscle, actively proliferated upon muscle injury and expressed not only several regulatory genes for muscle regeneration but also some mesenchymal lineage markers. CD31(-)CD45(-) SP cells showed the greatest myogenic potential among three SP sub-fractions, but indeed revealed mesenchymal potentials in vitro. These SP cells preferentially differentiated into myofibers after intramuscular transplantation in vivo. Our results revealed the heterogeneity of muscle SP cells and suggest that CD31(-)CD45(-) SP cells participate in muscle regeneration.
Uezumi
Akiyoshi
A
Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8502, Japan.
Ojima
Koichi
K
Fukada
So-ichiro
S
Ikemoto
Madoka
M
Masuda
Satoru
S
Miyagoe-Suzuki
Yuko
Y
Takeda
Shin'ichi
S
D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology; D005786:Gene Expression Regulation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000098:blood supply / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D009210:Myofibrils / Q000378:metabolism; D012038:Regeneration