Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation
Open accessAbstract
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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Injury is a well-established trigger of cellular de-differentiation.
“Injury is a well-established trigger of cellular de-differentiation, and the changes we observed are likely a consequence of human neurons adhering to this principle (Gu et al., 2020; Jopling et al., 2010; Poplawski et al., 2020; Renthal et al., 2020; Tzahor and Poss, 2017; Wagner et al., 2017).”
From Age-dependent instability of mature neuronal fate in induced neurons from Alzheimer’s patients (2021) · cites this paper as Jopling et al., 2010
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Self-citation
- 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
- Venue
- Nature
- Published
- 2010-03-25
- Volume
- 464
- Issue
- 7288
- Pages
- 606-609
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- 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
- 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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