A p53 based genetic tracing system to follow postnatal cardiomyocyte expansion in heart regeneration

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

doi:10.1242/dev.147827

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RESEARCH ARTICLE| 01 January 2017

A p53 based genetic tracing system to follow postnatal cardiomyocyte expansion in heart regeneration

In collection: Cardiovascular development and regeneration , Stem cells & regeneration

Qi Xiao,

Qi Xiao #

1

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

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Guoxin Zhang,

Guoxin Zhang #

1

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

2

State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Fudan University, Shanghai 200438, China

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Huijuan Wang,

Huijuan Wang

1

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

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Lai Chen,

Lai Chen

1

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

3

Jiangxi University of Traditional Chinese Medicine, 18 Yunwan Road, Nanchang, Jiangxi 330004, China

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Shuangshuang Lu,

Shuangshuang Lu

1

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

4

Sino-British Molecular Cancer Center of Zhengzhou University, Zhengzhou, China

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Dejing Pan,

Dejing Pan

1

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

5

Cambridge-Suda Genomic Research Center, Soochow University, 199 Renai Road, Suzhou 215123, China

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Geng Liu,

Geng Liu *

1

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 for correspondence: E-mail: zhongzhouyang@nju.edu.cn, E-mail: liug53@nju.edu.cn. Telephone: 0086-25-5864-1503; Fax:

0086-25-5864-1500

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Zhongzhou Yang

0000-0002-3272-5255

Zhongzhou Yang *

1

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 for correspondence: E-mail: zhongzhouyang@nju.edu.cn, E-mail: liug53@nju.edu.cn. Telephone: 0086-25-5864-1503; Fax:

0086-25-5864-1500

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Author and article information

Qi Xiao #

1

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

Guoxin Zhang #

1

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

2

State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Fudan University, Shanghai 200438, China

Huijuan Wang

1

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

Lai Chen

1

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

3

Jiangxi University of Traditional Chinese Medicine, 18 Yunwan Road, Nanchang, Jiangxi 330004, China

Shuangshuang Lu

1

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

4

Sino-British Molecular Cancer Center of Zhengzhou University, Zhengzhou, China

Dejing Pan

1

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

5

Cambridge-Suda Genomic Research Center, Soochow University, 199 Renai Road, Suzhou 215123, China

Geng Liu *

1

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

Zhongzhou Yang

https://orcid.org/0000-0002-3272-5255

*

1

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 for correspondence: E-mail: zhongzhouyang@nju.edu.cn, E-mail: liug53@nju.edu.cn. Telephone: 0086-25-5864-1503; Fax:

0086-25-5864-1500

#

Equal contribution

Received: 11 Dec 2016

Accepted: 04 Jan 2017

Online ISSN: 1477-9129

Print ISSN: 0950-1991

2017

http://www.biologists.com/user-licence-1-1/

Development dev.147827.

https://doi.org/10.1242/dev.147827

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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2017

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