Molecular signature of quiescent satellite cells in adult skeletal muscle
Molecular signature of quiescent satellite cells in adult skeletal muscle
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DOI：
10.1634/stemcells.2007-0019
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发表时间：
2007-01-01
期刊：
影响因子：
5.2
通讯作者：
Takedaa, Shin'ichi
中科院分区：
文献类型：
--
作者：
Fukada, So-Ichiro;Uezumi, Akiyoshi;Takedaa, Shin'ichi
骨骼肌卫星细胞在出生后肌肉的生长和再生中起着关键作用。为了研究卫星细胞的分子调控，我们直接制备了8-12周龄C57BL/6小鼠的卫星细胞，并进行了全基因组基因表达分析。与激活/循环的卫星细胞相比，静止的卫星细胞中507个基因高度上调。这些药物包括细胞周期的负性调节因子和肌源性抑制因子。基因集浓缩分析表明，静止的卫星细胞优先表达与细胞间黏附、细胞生长调节、细胞外基质形成、铜铁动态平衡和脂质运输相关的基因。此外，对差异表达基因的逆转录-聚合酶链式反应证实，降钙素受体(CTR)仅在休眠的卫星细胞中表达，而在激活的卫星细胞中不表达。此外，CTR mRNA在非肌源性细胞中几乎检测不到。因此，我们接下来检测了CTR在体内的表达。CTR在静止的卫星细胞上特异表达，而在肌肉再生过程中激活/增殖的卫星细胞上未见表达。在肌肉再生的后期，CTR阳性细胞重新出现在再生肌纤维的边缘。降钙素刺激延缓了静止卫星细胞的激活。我们的数据提供了CTR在静止的卫星细胞中的作用，并为进一步剖析卫星细胞的分子调控提供了坚实的支架。
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.