Berberoglu Michael A, Gallagher Thomas L, Morrow Zachary T, Talbot Jared C, Hromowyk Kimberly J, Tenente Inês M, Langenau David M, Amacher Sharon L
Departments of Molecular Genetics and Biological Chemistry and Pharmacology, The Ohio State University, Columbus, OH 43210, USA; Center for Muscle Health and Neuromuscular Disorders, The Ohio State University and Nationwide Children's Hospital, Columbus, OH 43210, USA.
Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA; Department of Molecular Pathology and Regenerative Medicine, Massachusetts General Hospital, Charlestown, MA 02129, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
Dev Biol. 2017 Apr 15;424(2):162-180. doi: 10.1016/j.ydbio.2017.03.004. Epub 2017 Mar 7.
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-like 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.
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。配对盒蛋白7（Pax7）和配对盒蛋白3（Pax3）转录因子是肌肉发育和再生所需的既定卫星细胞标志物，人们对识别调节卫星细胞增殖、分化和/或骨骼肌再生的其他因子有着浓厚兴趣。由于许多斑马鱼组织具有强大的再生能力，即使在成年斑马鱼中也是如此，我们正在探索成年斑马鱼骨骼肌的再生潜力。在此，我们表明成年斑马鱼骨骼肌含有与哺乳动物卫星细胞相似的细胞。成年斑马鱼类卫星细胞具有致密的异染色质，表达Pax7和Pax3，对损伤作出增殖反应，并在损伤后4 - 5天（dpi）显示出峰值生肌反应。此外，使用pax7a驱动的绿色荧光蛋白（GFP）报告基因，我们提供了证据表明类卫星细胞可能是新肌肉的来源。我们描述了几个特征，可从成年斑马鱼受伤肌肉中的周围纤维中可靠地识别新形成的肌纤维，以此替代区分哺乳动物再生肌纤维的中央成核现象。这些特征包括两种已知调节胚胎肌肉发育和功能的RNA结合蛋白Rbfox2和Rbfoxl1在类卫星细胞和再生肌纤维中的部分重叠表达。最后，通过分析pax7a；pax7b双突变斑马鱼，我们表明Pax7对成年骨骼肌修复是必需的，就像在小鼠中一样。
