Fukada So-ichiro, Uezumi Akiyoshi, Ikemoto Madoka, Masuda Satoru, Segawa Masashi, Tanimura Naoki, Yamamoto Hiroshi, Miyagoe-Suzuki Yuko, Takeda Shin'ichi
Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8502, Japan.
Stem Cells. 2007 Oct;25(10):2448-59. doi: 10.1634/stemcells.2007-0019. Epub 2007 Jun 28.
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.
骨骼肌卫星细胞在出生后肌肉生长和再生中起关键作用。为了研究卫星细胞的分子调控，我们直接从8至12周龄的C57BL/6小鼠中制备卫星细胞，并进行全基因组基因表达分析。与活化/增殖的卫星细胞相比，507个基因在静止卫星细胞中高度上调。这些基因包括细胞周期负调控因子和成肌抑制因子。基因集富集分析表明，静止卫星细胞优先表达参与细胞间粘附、细胞生长调控、细胞外基质形成、铜和铁稳态以及脂质运输的基因。此外，对差异表达基因进行的逆转录-聚合酶链反应证实，降钙素受体（CTR）仅在休眠卫星细胞中表达，而在活化卫星细胞中不表达。此外，在非肌细胞中几乎检测不到CTR mRNA。因此，我们接下来检测了CTR在体内的表达。CTR在静止卫星细胞上特异性表达，但在肌肉再生过程中，活化/增殖的卫星细胞上未发现其表达。在肌肉再生后期，CTR阳性细胞重新出现在再生肌纤维的边缘。降钙素刺激延迟了静止卫星细胞的活化。我们的数据揭示了CTR在静止卫星细胞中的作用，并为进一步剖析卫星细胞的分子调控提供了坚实的框架。潜在利益冲突的披露见本文末尾。
