Satellite-like cells contribute to pax7-dependent skeletal muscle repair in adult zebrafish.

Satellite-like cells contribute to pax7-dependent skeletal muscle repair in adult zebrafish.
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DOI:
10.1016/j.ydbio.2017.03.004
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发表时间:
2017-04-15
影响因子:
2.7
通讯作者:
Amacher SL
Amacher SL
中科院分区:
生物学3区
文献类型:
--
作者:
Berberoglu MA;Gallagher TL;Morrow ZT;Talbot JC;Hromowyk KJ;Tenente IM;Langenau DM;Amacher SL

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卫星细胞,也被称为肌肉干细胞,负责哺乳动物骨骼肌的生长和修复。PAX7和Pax3转录因子是肌肉发育和再生所需的已建立的卫星细胞标记,人们对识别其他调控卫星细胞增殖、分化和/或骨骼肌再生的因子非常感兴趣。由于许多斑马鱼组织具有强大的再生能力,即使是成年斑马鱼,我们也在探索成年斑马鱼骨骼肌的再生潜力。在这里,我们展示了成年斑马鱼骨骼肌含有类似于哺乳动物卫星细胞的细胞。成体斑马鱼卫星样细胞异染色质密度高,表达Pax7和Pax3,损伤后增殖,伤后4~5d出现生肌反应高峰。此外,使用pax7a驱动的GFP记者,我们提出了卫星样细胞可能是新肌肉来源的证据。代替区分哺乳动物再生肌纤维的中心成核,我们描述了几个特征,这些特征有力地识别了受伤的成年斑马鱼肌肉中新形成的肌纤维和周围的纤维。这些特征包括在卫星细胞中部分重叠表达和再生两个RNA结合蛋白RBFox2和Rbfoxl1的肌纤维,已知这两个蛋白调控胚胎肌肉的发育和功能。最后,通过分析pax7a;pax7b双突变斑马鱼,我们证明了Pax7是成年骨骼肌修复所必需的,就像在小鼠身上一样。
Satellite cells, also known as muscle stem cells, are responsible for skeletal muscle growth and repair in mammals. Pax7 and Pax3 transcription factors are established satellite cell markers required for muscle development and regeneration, and there is great interest in identifying additional factors that regulate satellite cell proliferation, differentiation, and/or skeletal muscle regeneration. Due to the powerful regenerative capacity of many zebrafish tissues, even in adults, we are exploring the regenerative potential of adult zebrafish skeletal muscle. Here, we show that adult zebrafish skeletal muscle contains cells similar to mammalian satellite cells. Adult zebrafish satellite-like cells have dense heterochromatin, express Pax7 and Pax3, proliferate in response to injury, and show peak myogenic responses 4–5 days post-injury (dpi). Furthermore, using a pax7a-driven GFP reporter, we present evidence implicating satellite-like cells as a possible source of new muscle. In lieu of central nucleation, which distinguishes regenerating myofibers in mammals, we describe several characteristics that robustly identify newly-forming myofibers from surrounding fibers in injured adult zebrafish muscle. These characteristics include partially overlapping expression in satellite cells and regenerating myofibers of two RNA-binding proteins Rbfox2 and Rbfoxl1, known to regulate embryonic muscle development and function. Finally, by analyzing pax7a; pax7b double mutant zebrafish, we show that Pax7 is required for adult skeletal muscle repair, as it is in the mouse.