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First published online June 28, 2007
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2007-0019v1
25/10/2448    most recent
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Submitted on January 8, 2007
Accepted on June 19, 2007

TISSUE-SPECIFIC STEM CELLS

Molecular Signature of Quiescent Satellite Cells In Adult Skeletal Muscle

So ichiro Fukada 1, Akiyoshi Uezumi 1, Madoka Ikemoto 1, Satoru Masuda 1, Masashi Segawa 2, Naoki Tanimura 3, Hiroshi Yamamoto 2, Yuko Miyagoe-Suzuki 1*, Shin'ichi Takeda 1

1 Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8502, Japan
2 Department of Immunology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan
3 Bio and Nano Technologies, Science and Technology Division, Mizuho Information & Research Institute, Inc., 2-3 Kanda-Nishikicho, Chiyoda-ku, Tokyo 101-8443, Japan

* To whom correspondence should be addressed. E-mail: miyagoe{at}ncnp.go.jp.


   Abstract

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 up-regulated in quiescent satellite cells. These include 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, RT-PCR 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 non-myogenic 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.

Key Words. FACS, Microarray, Quiescence, Muscle satellite cells, Calcitonin receptor




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