A population of Pax7-expressing muscle progenitor cells show differential responses to muscle injury dependent on developmental stage and injury extent.
A population of Pax7-expressing muscle progenitor cells show differential responses to muscle injury dependent on developmental stage and injury extent.
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DOI：
10.3389/fnagi.2015.00161
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发表时间：
2015
影响因子：
4.8
通讯作者：
Knight RD
中科院分区：
文献类型：
--
作者：
Knappe S;Zammit PS;Knight RD
脊椎动物骨骼肌的再生是通过激活静止的表达PAX7的前体细胞来修复和替换受损的肌纤维来实现的。我们在斑马鱼中建立了一个机械损伤模式，以确定发育阶段和损伤大小是否影响骨骼肌的再生动力学。我们发现，无论是小的局灶性损伤，还是影响整个肌节的大损伤，都会导致myf5和mygenin的表达，而这种表达在较大的幼虫中会延长，表明再生过程较慢。我们利用pax7a：EGFP转基因细胞系研究了一组肌肉中表达Pax7的细胞的内源性行为，发现在受精后5至7天(DPF)，GFP+细胞在肌节中的迁移显著减少。在单个小肌节损伤后，GFP+细胞通过延长突起做出反应，然后迁移到受损的肌纤维。此外，在4个DPF幼虫中，这些细胞对伤害的反应比7个DPF幼虫更快。有趣的是，在小损伤修复后，我们没有看到GFP+的肌纤维，这表明在这种损伤情况下，pax7a表达的细胞对肌纤维的形成没有贡献。相反，在广泛的单个肌节损伤后，可以观察到大量的GFP+肌纤维。两种损伤模型均伴有增殖的GFP+细胞数量增加，在损伤后4dpf的幼虫比7dpf的幼虫更明显。这表明，在这些早期阶段，存在着有趣的发育差异。我们的数据还表明，表达pax7a的肌祖细胞在骨骼肌再生过程中扮演的角色存在着有趣的差异，这可能反映了肌肉损伤的程度。
Skeletal muscle regeneration in vertebrates occurs by the activation of quiescent progenitor cells that express pax7 to repair and replace damaged myofibers. We have developed a mechanical injury paradigm in zebrafish to determine whether developmental stage and injury size affect the regeneration dynamics of skeletal muscle. We found that both small focal injuries, and large injuries affecting the entire myotome, lead to expression of myf5 and myogenin, which was prolonged in older larvae, indicating a slower process of regeneration. We characterized the endogenous behavior of a population of muscle-resident Pax7-expressing cells using a pax7a:eGFP transgenic line and found that GFP+ cell migration in the myotome dramatically declined between 5 and 7 days post-fertilization (dpf). Following a small single myotome injury, GFP+ cells responded by extending processes, before migrating to the injured myofibers. Furthermore, these cells responded more rapidly to injury in 4 dpf larvae compared to 7 dpf. Interestingly, we did not see GFP+ myofibers after repair of small injuries, indicating that pax7a-expressing cells did not contribute to myofiber formation in this injury context. On the contrary, numerous GFP+ myofibers could be observed after an extensive single myotome injury. Both injury models were accompanied by an increased number of proliferating GFP+ cells, which was more pronounced in larvae injured at 4 dpf than 7 dpf. This indicates intriguing developmental differences, at these early ages. Our data also suggests an interesting disparity in the role that pax7a-expressing muscle progenitor cells play during skeletal muscle regeneration, which may reflect the extent of muscle damage.