A p53-based genetic tracing system to follow postnatal cardiomyocyte expansion in heart regeneration
A p53-based genetic tracing system to follow postnatal cardiomyocyte expansion in heart regeneration
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DOI：
10.1242/dev.147827
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发表时间：
2017-02-15
期刊：
影响因子：
4.6
通讯作者：
Yang, Zhongzhou
中科院分区：
文献类型：
--
作者：
Xiao, Qi;Zhang, Guoxin;Yang, Zhongzhou
在心脏再生领域，出生后小鼠心肌细胞的增殖潜力正在进行深入研究。然而，仅仅依靠增殖标记物的免疫染色，心肌细胞的长期增殖动力学和潜力不能容易地解决。以前，我们发现p53启动子驱动的报告基因主要标记小鼠的增殖谱系。在此，我们建立了一个基于p53基因的遗传追踪系统，以研究出生后心肌细胞增殖和心脏再生。通过选择性地追踪增殖的心肌细胞，p53（+）心肌细胞克隆性扩增的差异模式在新生儿，青少年和成人阶段被揭示。此外，p53（+）谱系心肌细胞的百分比在第一个月持续增加。此外，这些细胞对心脏损伤迅速做出反应，并极大地促进了心肌的补充。因此，本研究揭示了出生后心肌细胞和心脏修复中复杂的增殖动力学，并为研究出生后心脏更新和再生提供了一种新的遗传示踪策略。
In the field of heart regeneration, the proliferative potential of cardiomyocytes in postnatal mice is under intense investigation. However, solely relying on immunostaining of proliferation markers, the long-term proliferation dynamics and potential of the cardiomyocytes cannot be readily addressed. Previously, we found that a p53 promoter-driving reporter predominantly marked the proliferating lineages in mice. Here, we established a p53-based genetic tracing system to investigate postnatal cardiomyocyte proliferation and heart regeneration. By selectively tracing proliferative cardiomyocytes, a differential pattern of clonal expansion in p53(+) cardiac myocytes was revealed in neonatal, adolescent and adult stages. In addition, the percentage of p53(+) lineage cardiomyocytes increased continuously in the first month. Furthermore, these cells rapidly responded to heart injury and greatly contributed to the replenished myocardium. Therefore, this study reveals complex proliferating dynamics in postnatal cardiomyocytes and heart repair, and provides a novel genetic tracing strategy for studying postnatal cardiac turnover and regeneration.