Doublecortin marks a new population of transiently amplifying muscle progenitor cells and is required for myofiber maturation during skeletal muscle regeneration
Doublecortin marks a new population of transiently amplifying muscle progenitor cells and is required for myofiber maturation during skeletal muscle regeneration
复制标题
DOI：
10.1242/dev.112557
复制
发表时间：
2015-01-01
期刊：
影响因子：
4.6
通讯作者：
Fukada, So-ichiro
中科院分区：
文献类型：
--
作者：
Ogawa, Ryo;Ma, Yuran;Fukada, So-ichiro
肌肉卫星细胞对肌肉再生是必不可少的，但其子细胞的功能多样性尚不清楚。在这里，我们发现在肌纤维成熟过程中，许多Pax7(+)MyoD（-）细胞位于基底膜的下方和外部。这些Pax7(+)MyoD（-）细胞大多数不是自我更新的卫星细胞，但与Pax7(+)MyoD（+）成肌细胞（经典子细胞）具有不同的增殖和分化潜力，并且通过双皮质素（Dcx）基因的表达特异性标记。移植和谱系追踪实验表明，表达Dcx的细胞起源于静止的卫星细胞，微环境在成肌细胞中诱导Dcx。Dcx的表达似乎是肌纤维成熟所必需的，因为Dcx缺陷小鼠表现出由于肌核数量减少而导致的肌纤维成熟受损。此外，体外和体内研究表明，Dcx在肌源性细胞中的一个功能是加速细胞运动。这些结果表明，Dcx是Pax7(+)MyoD（-）亚群的新标记物，它有助于肌肉再生过程中肌纤维的成熟。
Muscle satellite cells are indispensable for muscle regeneration, but the functional diversity of their daughter cells is unknown. Here, we show that many Pax7(+)MyoD(-) cells locate both beneath and outside the basal lamina during myofiber maturation. A large majority of these Pax7(+)MyoD(-) cells are not self-renewed satellite cells, but have different potentials for both proliferation and differentiation from Pax7(+)MyoD(+) myoblasts (classical daughter cells), and are specifically marked by expression of the doublecortin (Dcx) gene. Transplantation and lineage-tracing experiments demonstrated that Dcx-expressing cells originate from quiescent satellite cells and that the microenvironment induces Dcx in myoblasts. Expression of Dcx seems to be necessary for myofiber maturation because Dcx-deficient mice exhibited impaired myofiber maturation resulting from a decrease in the number of myonuclei. Furthermore, in vitro and in vivo studies suggest that one function of Dcx in myogenic cells is acceleration of cell motility. These results indicate that Dcx is a new marker for the Pax7(+)MyoD(-) subpopulation, which contributes to myofiber maturation during muscle regeneration.