A p53 based genetic tracing system to follow postnatal cardiomyocyte expansion in heart regeneration [RESEARCH ARTICLE]

Qi Xiao, Guoxin Zhang, Huijuan Wang, Lai Chen, Shuangshuang Lu, Dejing Pan, Geng Liu, and Zhongzhou Yang

For heart regeneration, the proliferative potential of cardiomyocytes in postnatal mice is under intense investigations. 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 the 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 displayed continuous increase in the first month. Furthermore, these cells rapidly responded to heart injury and greatly contributed to replenished myocardium. Therefore, this study revealed complex proliferating dynamics in postnatal cardiomyocytes and heart repair, and provided a novel genetic tracing strategy to study postnatal cardiac turnover and regeneration.

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