Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation
By C. Jopling, Eduard Sleep, Marina Raya, M. Martí, Á. Raya, J. Belmonte. Nature, 2010
1,343 citations recorded by the source corpus.
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.
Subfields: Electrical and Electronic Engineering, Epidemiology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/7f1dfb3b8298faa223d8eec3fe7e542cfe64bff2
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Citations in the corpus
- Hippo pathway effector Yap promotes cardiac regeneration (2013, background): “Heart regeneration in zebrafish and neonatal mice is correlated with global activation of cardiomyocyte proliferation throughout the injured organ (13, 18, 19).”
- Mammalian Heart Renewal by Preexisting Cardiomyocytes (2012, positive): “Such an explanation excludes a role for endogenous progenitors in cardiac repair and would be consistent with data emerging from lower vertebrates 8,26 and the neonatal mouse 27 in which preexisting cardiomyocytes are the cellular source for cardiomyocyte repletion.”
- Regulation of neonatal and adult mammalian heart regeneration by the miR-15 family (2012, background): “Cardiomyocyte proliferation appears to be the major cellular mechanism driving cardiac regeneration in neonatalmice (8) and adult zebrafish (9, 10).”
- Dedifferentiation, transdifferentiation and reprogramming: three routes to regeneration (2011, background): “During this process, differentiated cardiomyocytes that are still present in the heart dedifferentiate and proliferate to regenerate the missing tissu”
- Production of De Novo Cardiomyocytes: Human Pluripotent Stem Cell Differentiation and Direct Reprogramming (2012, neutral): “This regeneration 16 Cell Stem Cell 10, January 6, 2012 ª2012 Elsevier Inc. occurs through the proliferation and dedifferentiation of cardiomyocytes (Jopling et al., 2010), and similar regeneration has been demonstrated in mice, but only within the first week postpartum (Porrello et al., 2011).”
- Cardiac fibrosis in myocardial infarction—from repair and remodeling to regeneration (2016, background): “Collagens are synthesized and secreted by fibroblasts and myofibroblasts as collagen precursors and acquire their mature fibrillar form after proteolytic cleavage by collagen proteinases, association with matricellular proteins, and self-assembly to fibrils.”