Molecular signature of quiescent satellite cells in adult skeletal muscle.
Skeletal muscle satellite cells play key roles in postnatal muscle growth and regeneration. To study molecular regulation of satellite cells, we directly prepared satellite cells from 8- to 12-week-old C57BL/6 mice and performed genome-wide gene expression analysis. Compared with activated/cycling satellite cells, 507 genes were highly upregulated in quiescent satellite cells. These included negative regulators of cell cycle and myogenic inhibitors. Gene set enrichment analysis revealed that quiescent satellite cells preferentially express the genes involved in cell-cell adhesion, regulation of cell growth, formation of extracellular matrix, copper and iron homeostasis, and lipid transportation. Furthermore, reverse transcription-polymerase chain reaction on differentially expressed genes confirmed that calcitonin receptor (CTR) was exclusively expressed in dormant satellite cells but not in activated satellite cells. In addition, CTR mRNA is hardly detected in nonmyogenic cells. Therefore, we next examined the expression of CTR in vivo. CTR was specifically expressed on quiescent satellite cells, but the expression was not found on activated/proliferating satellite cells during muscle regeneration. CTR-positive cells reappeared at the rim of regenerating myofibers in later stages of muscle regeneration. Calcitonin stimulation delayed the activation of quiescent satellite cells. Our data provide roles of CTR in quiescent satellite cells and a solid scaffold to further dissect molecular regulation of satellite cells. Disclosure of potential conflicts of interest is found at the end of this article.
Fukada
So-ichiro
S
Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8502, Japan.
Uezumi
Akiyoshi
A
Ikemoto
Madoka
M
Masuda
Satoru
S
Segawa
Masashi
M
Tanimura
Naoki
N
Yamamoto
Hiroshi
H
Miyagoe-Suzuki
Yuko
Y
Takeda
Shin'ichi
S
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000235:genetics; D015415:Biomarkers; D002116:Calcitonin / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics; D002454:Cell Differentiation; D002455:Cell Division / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008810:Mice, Inbred C57BL; D024510:Muscle Development / Q000235:genetics*; D009124:Muscle Proteins / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D018482:Muscle, Skeletal / Q000502:physiology; D018006:Myogenic Regulatory Factors / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D018003:Receptors, Calcitonin / Q000096:biosynthesis / Q000235:genetics; D012038:Regeneration / Q000235:genetics; D032496:Satellite Cells, Skeletal Muscle / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; D009124:Muscle Proteins; D018006:Myogenic Regulatory Factors; D012333:RNA, Messenger; D018003:Receptors, Calcitonin; D002116:Calcitonin