Calcitonin Receptor Signaling Inhibits Muscle Stem Cells from Escaping the Quiescent State and the Niche
Calcitonin Receptor Signaling Inhibits Muscle Stem Cells from Escaping the Quiescent State and the Niche
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DOI：
10.1016/j.celrep.2015.08.083
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发表时间：
2015-10-13
期刊：
影响因子：
8.8
通讯作者：
Fukada, So-ichiro
中科院分区：
文献类型：
--
作者：
Yamaguchi, Masahiko;Watanabe, Yoko;Fukada, So-ichiro
降钙素受体（Calcr）在成体肌肉干细胞（肌肉卫星细胞[MuSC]）中表达。为了阐明Calcr的作用，我们从成年MuSC中有条件地耗尽Calcr，并发现肌肉损伤后的再生受损与Calcr条件性敲除（cKO）小鼠中MuSC数量的减少相关。Calcr信号通过cAMP-PKA途径维持MuSC休眠，但对未分化状态下MuSC的肌源性分化没有影响。Calcr-cKO小鼠中的异常静止状态导致MuSC池通过细胞凋亡减少。此外，在Calcr-cKO小鼠中发现MuSC在其小生境之外，证明了细胞重新定位。这种从板层下小生境的出现被Calcr下游的CalcrcAMP-PKA和Calcr-cAMP-Epac途径阻止。总而言之，研究结果表明，Calcr通过保持MuSC处于静止状态和它们的位置，维持MuSC池来发挥其作用。
Calcitonin receptor (Calcr) is expressed in adult muscle stem cells (muscle satellite cells [MuSCs]). To elucidate the role of Calcr, we conditionally depleted Calcr from adult MuSCs and found that impaired regeneration after muscle injury correlated with the decreased number of MuSCs in Calcr-conditional knockout (cKO) mice. Calcr signaling maintained MuSC dormancy via the cAMP-PKA pathway but had no impact on myogenic differentiation of MuSCs in an undifferentiated state. The abnormal quiescent state in Calcr-cKO mice resulted in a reduction of the MuSC pool by apoptosis. Furthermore, MuSCs were found outside their niche in Calcr-cKO mice, demonstrating cell relocation. This emergence from the sublaminar niche was prevented by the CalcrcAMP-PKA and Calcr-cAMP-Epac pathways downstream of Calcr. Altogether, the findings demonstrated that Calcr exerts its effect specifically by keeping MuSCs in a quiescent state and in their location, maintaining the MuSC pool.