Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, OX1 3PT, UK.
Bioinfo, Plantagenet, ON K0B 1L0, Canada.
Cell Rep. 2018 Nov 20;25(8):1997-2007.e7. doi: 10.1016/j.celrep.2018.10.072.
Although Astyanax mexicanus surface fish regenerate their hearts after injury, their Pachón cave-dwelling counterparts cannot and, instead, form a permanent fibrotic scar, similar to the human heart. Myocardial proliferation peaks at similar levels in both surface fish and Pachón 1 week after injury. However, in Pachón, this peak coincides with a strong scarring and immune response, and ultimately, cavefish cardiomyocytes fail to replace the scar. We identified lrrc10 to be upregulated in surface fish compared with Pachón after injury. Similar to cavefish, knockout of lrrc10 in zebrafish impairs heart regeneration without affecting wound cardiomyocyte proliferation. Furthermore, using quantitative trait locus (QTL) analysis, we have linked the degree of heart regeneration to three loci in the genome, identifying candidate genes fundamental to the difference between scarring and regeneration. Our study provides evidence that successful heart regeneration entails a delicate interplay between cardiomyocyte proliferation and scarring.
虽然墨西哥脂鲤体表鱼在受伤后可以再生心脏，但它们的帕雄洞穴鱼却不能，而是形成永久性的纤维疤痕，类似于人类心脏。心肌增殖在受伤后 1 周时在体表鱼和帕雄鱼中达到相似的峰值。然而，在帕雄鱼中，这个峰值与强烈的疤痕和免疫反应同时出现，最终，洞穴鱼心肌细胞无法替代疤痕。我们发现，与帕雄鱼相比，体表鱼在受伤后 lrrc10 上调。与洞穴鱼相似，敲除斑马鱼的 lrrc10 会损害心脏再生，而不影响伤口心肌细胞增殖。此外，我们通过数量性状基因座 (QTL) 分析，将心脏再生程度与基因组中的三个基因座联系起来，确定了与疤痕形成和再生之间差异相关的候选基因。我们的研究提供了证据，表明成功的心脏再生需要心肌细胞增殖和疤痕形成之间的微妙相互作用。
