title: A p53-based genetic tracing system to follow postnatal cardiomyocyte expansion in heart regeneration.
abstract: 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 ap53promoter-driving reporter predominantly marked the proliferating lineages in mice. Here, we established ap53-based genetic tracing system to investigate postnatal cardiomyocyte proliferation and heart regeneration. By selectively tracing proliferative cardiomyocytes, a differential pattern of clonal expansion inp53+cardiac myocytes was revealed in neonatal, adolescent and adult stages. In addition, the percentage ofp53+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.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing 210061, China.|State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Fudan University, Shanghai 200438, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Xiao
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing 210061, China.
authors.forename: Guoxin
authors.initials: G
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing 210061, China.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing 210061, China.|Jiangxi University of Traditional Chinese Medicine, 18 Yunwan Road, Nanchang, Jiangxi 330004, China.
authors.forename: Lai
authors.initials: L
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing 210061, China.|Sino-British Molecular Cancer Center of Zhengzhou University, Zhengzhou, China.
authors.forename: Shuangshuang
authors.initials: S
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing 210061, China.|Cambridge-Suda Genomic Research Center, Soochow University, 199 Renai Road, Suzhou 215123, China.
authors.forename: Dejing
authors.initials: D
authors.lastname: Pan
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing 210061, China zhongzhouyang@nju.edu.cn liug53@nju.edu.cn.
authors.forename: Geng
authors.initials: G
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing 210061, China zhongzhouyang@nju.edu.cn liug53@nju.edu.cn.|State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Fudan University, Shanghai 200438, China.
authors.forename: Zhongzhou
authors.identifier: 0000-0002-3272-5255
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000818:Animals; D019070:Cell Lineage; D049109:Cell Proliferation; D003331:Coronary Vessels / Q000502:physiology; D004195:Disease Models, Animal; D017930:Genes, Reporter; D016158:Genes, p53; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006321:Heart / Q000502:physiology*; D006352:Heart Ventricles / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D051379:Mice; D008822:Mice, Transgenic; D009203:Myocardial Infarction; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism*; D012038:Regeneration / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53; D049452:Green Fluorescent Proteins
keywords: Cardiomyocyte; Cell proliferation; Heart regeneration; Lineage tracing; Mouse; p53