An absolute requirement for Pax7-positive satellite cells in acute injury-induced skeletal muscle regeneration
An absolute requirement for Pax7-positive satellite cells in acute injury-induced skeletal muscle regeneration
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DOI：
10.1242/dev.067595
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发表时间：
2011-09-01
期刊：
影响因子：
4.6
通讯作者：
Fan, Chen-Ming
中科院分区：
文献类型：
--
作者：
Lepper, Christoph;Partridge, Terence A.;Fan, Chen-Ming
骨骼肌组织为所有脊椎动物的运动提供机械力。急性生理创伤和生理应激容易造成损伤。为了解决这个问题，它具有快速有效修复的巨大能力，这种能力被广泛认为是由位于肌纤维质膜和基膜之间的卫星细胞完成的。细胞移植和谱系追踪研究表明，表达Pax7（+）的卫星细胞可以在几次急性损伤后反复修复受损的肌肉组织。这些发现为Pax7（+）细胞是肌肉干细胞提供了证据。然而，据报道，其他来源的干细胞在移植到肌肉中时也有助于肌纤维的形成，这就质疑卫星细胞是否是肌肉再生的唯一干细胞来源。在这里，我们设计了Pax7（+）细胞的基因消融，以测试是否有其他来源的细胞在急性损伤后对肌肉再生有显著贡献。我们发现Pax7+细胞的这种消除完全阻断了胫骨前肌损伤后或将指长伸肌移植到裸鼠体内后的再生肌发生。由于Pax7在卫星细胞中特异性表达，我们得出结论，它们对急性损伤诱导的肌肉再生至关重要。其他来源的干细胞是否有重要作用还有待确定。我们的结果对肌肉干细胞治疗的意义进行了讨论。
Skeletal muscle tissue provides mechanical force for locomotion of all vertebrate animals. It is prone to damage from acute physical trauma and physiological stress. To cope with this, it possesses a tremendous capacity for rapid and effective repair that is widely held to be accomplished by the satellite cells lying between the muscle fiber plasmalemma and the basement membrane. Cell transplantation and lineage-tracing studies have demonstrated that Pax7-expressing (Pax7(+)) satellite cells can repair damaged muscle tissue repeatedly after several bouts of acute injury. These findings provided evidence that Pax7(+) cells are muscle stem cells. However, stem cells from a variety of other origins are also reported to contribute to myofibers upon engraftment into muscles, questioning whether satellite cells are the only stem cell source for muscle regeneration. Here, we have engineered genetic ablation of Pax7(+) cells to test whether there is any significant contribution to muscle regeneration after acute injury from cells other than this source. We find that such elimination of Pax7+ cells completely blocks regenerative myogenesis either following injury to the tibialis anterior (TA) muscle or after transplantation of extensor digitorum longus (EDL) muscles into nude mice. As Pax7 is specifically expressed in satellite cells, we conclude that they are essential for acute injury-induced muscle regeneration. It remains to be established whether there is any significant role for stem cells of other origins. The implications of our results for muscle stem cell-based therapy are discussed.