对心脏衰竭患者使用干细胞疗法所存在的障碍包括:难以确保心脏祖细胞分化成功能性心室心肌细胞,以及难以确保能将分化的细胞输送和集成到患者的“心室肌”中。Neil Chi及其同事研究了特定心肌细胞类型在斑马鱼胚胎心脏中分化成密切相关的、但却截然不同的细胞类型的能力。他们发现,分化的心房心肌细胞在心脏受伤时能转变成心室心肌细胞,而且Notch信号作用通道诱导这种再生。这项研究将内源性心脏细胞类群确定为心室再生的一个潜在来源。(生物谷Bioon.com)
生物谷推荐英文摘要:
Nature doi:10.1038/nature12322
In vivo cardiac reprogramming contributes to zebrafish heart regeneration
Ruilin Zhang,Peidong Han,Hongbo Yang,Kunfu Ouyang,Derek Lee,Yi-Fan Lin,Karen Ocorr,Guson Kang,Ju Chen,Didier Y. R. Stainier,Deborah Yelon& Neil C. Chi
Despite current treatment regimens, heart failure remains the leading cause of morbidity and mortality in the developed world due to the limited capacity of adult mammalian ventricular cardiomyocytes to divide and replace ventricular myocardium lost from ischaemia-induced infarct. Hence there is great interest to identify potential cellular sources and strategies to generate new ventricular myocardium. Past studies have shown that fish and amphibians and early postnatal mammalian ventricular cardiomyocytes can proliferate to help regenerate injured ventricles; however, recent studies have suggested that additional endogenous cellular sources may contribute to this overall ventricular regeneration. Here we have developed, in the zebrafish (Danio rerio), a combination of fluorescent reporter transgenes, genetic fate-mapping strategies and a ventricle-specific genetic ablation system to discover that differentiated atrial cardiomyocytes can transdifferentiate into ventricular cardiomyocytes to contribute to zebrafish cardiac ventricular regeneration. Using in vivo time-lapse and confocal imaging, we monitored the dynamic cellular events during atrial-to-ventricular cardiomyocyte transdifferentiation to define intermediate cardiac reprogramming stages. We observed that Notch signalling becomes activated in the atrial endocardium following ventricular ablation, and discovered that inhibiting Notch signalling blocked the atrial-to-ventricular transdifferentiation and cardiac regeneration. Overall, these studies not only provide evidence for the plasticity of cardiac lineages during myocardial injury, but more importantly reveal an abundant new potential cardiac resident cellular source for cardiac ventricular regeneration.