Cited by 1,333Congenital heart defects researchZebrafish Biomedical Research ApplicationsNeurogenesis and neuroplasticity mechanisms

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Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation

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Jopling, Chris, Sleep, Eduard, Raya, Marina, Martí, Mercè, Raya, Angel, Belmonte, Juan Carlos Izpisúa·2010·Nature

DOI 10.1038/nature08899PMC PMC2846535

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Abstract

Although mammalian hearts show almost no ability to regenerate, there is a growing initiative to determine whether existing cardiomyocytes or progenitor cells can be coaxed into eliciting a regenerative response. In contrast to mammals, several non-mammalian vertebrate species are able to regenerate their hearts, including the zebrafish, which can fully regenerate its heart after amputation of up to 20% of the ventricle. To address directly the source of newly formed cardiomyocytes during zebrafish heart regeneration, we first established a genetic strategy to trace the lineage of cardiomyocytes in the adult fish, on the basis of the Cre/lox system widely used in the mouse. Here we use this system to show that regenerated heart muscle cells are derived from the proliferation of differentiated cardiomyocytes. Furthermore, we show that proliferating cardiomyocytes undergo limited dedifferentiation characterized by the disassembly of their sarcomeric structure, detachment from one another and the expression of regulators of cell-cycle progression. Specifically, we show that the gene product of polo-like kinase 1 (plk1) is an essential component of cardiomyocyte proliferation during heart regeneration. Our data provide the first direct evidence for the source of proliferating cardiomyocytes during zebrafish heart regeneration and indicate that stem or progenitor cells are not significantly involved in this process.

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Authors: Jopling, C., Sleep, E., Raya, M., Martí, M., Raya, A., & Belmonte, J. C. I.
Affiliations: Center of Regenerative Medicine in Barcelona (ES)
Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (ES)
Salk Institute for Biological Studies (US)
Corresponding author: Belmonte, Juan Carlos Izpisúa
ORCID: Jopling, Chris
Belmonte, Juan Carlos Izpisúa
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2010-03-25
Volume: 464
Issue: 7288
Pages: 606-609
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature08899
PMC: PMC2846535
OpenAlex: W1998457769
Cited by: 1,333
References: 25
Citations by year: 2026: 54 · 2025: 73 · 2024: 53 · 2023: 59 · 2022: 85 · 2021: 104 · 2020: 98 · 2019: 83 · 2018: 99 · 2017: 74 · 2016: 82 · 2015: 88 · 2014: 82 · 2013: 93 · 2012: 101
FWCI: 38.85
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Funders: G. Harold and Leila Y. Mathers Foundation
Ministerio de Ciencia e Innovación
National Heart, Lung, and Blood Institute (R33HL088293)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Zebrafish Biomedical Research Applications
Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords: zebrafish heart regeneration, cardiomyocyte dedifferentiation, cardiomyocyte proliferation, myocardial infarction, PLK1, sarcomere disassembly, cell cycle regulators, cardiac progenitor cells
MeSH terms: Polo-Like Kinase 1, Animals, Gene Expression Regulation, Heart, Proto-Oncogene Proteins, Regeneration, Sarcomeres, Zebrafish, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Cell Lineage, Myocytes, Cardiac, Cell Proliferation, Cell Dedifferentiation

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Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation

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