Oudhoff Hendrik, Hisler Vincent, Baumgartner Florian, Rees Lana, Grepper Dogan, Jaźwińska Anna
Department of Biology, University of Fribourg, Chemin du Musée 10, 1700, Fribourg, Switzerland.
NPJ Regen Med. 2024 Feb 20;9(1):8. doi: 10.1038/s41536-024-00351-5.
Skeletal muscles can regenerate after minor injuries, but severe structural damage often leads to fibrosis in mammals. Whether adult zebrafish possess the capacity to reproduce profoundly destroyed musculature remains unknown. Here, a new cryoinjury model revealed that several myomeres efficiently regenerated within one month after wounding the zebrafish caudal peduncle. Wound clearance involved accumulation of the selective autophagy receptor p62, an immune response and Collagen XII deposition. New muscle formation was associated with proliferation of Pax7 expressing muscle stem cells, which gave rise to MyoD1 positive myogenic precursors, followed by myofiber differentiation. Monitoring of slow and fast muscles revealed their coordinated replacement in the superficial and profound compartments of the myomere. However, the final boundary between the muscular components was imperfectly recapitulated, allowing myofibers of different identities to intermingle. The replacement of connective with sarcomeric tissues required TOR signaling, as rapamycin treatment impaired new muscle formation, leading to persistent fibrosis. The model of zebrafish myomere restoration may provide new medical perspectives for treatment of traumatic injuries.
骨骼肌在轻度损伤后能够再生，但在哺乳动物中，严重的结构损伤往往会导致纤维化。成年斑马鱼是否具备再生严重受损肌肉组织的能力仍是未知的。在此，一种新的冷冻损伤模型显示，斑马鱼尾柄受伤后，几个肌节在一个月内有效再生。伤口愈合涉及选择性自噬受体p62的积累、免疫反应和Ⅻ型胶原蛋白沉积。新肌肉的形成与表达Pax7的肌肉干细胞增殖有关，这些干细胞产生MyoD1阳性的肌源性前体细胞，随后是肌纤维分化。对慢肌和快肌的监测显示，它们在肌节的浅层和深层区域协同替换。然而，肌肉成分之间的最终边界并未完全重现，使得不同类型的肌纤维相互交织。用肌节组织替代结缔组织需要TOR信号传导，因为雷帕霉素处理会损害新肌肉的形成，导致持续性纤维化。斑马鱼肌节修复模型可能为创伤性损伤的治疗提供新的医学视角。
