PUBLICATION

Myocardial Polyploidization Creates a Barrier to Heart Regeneration in Zebrafish

Authors
González-Rosa, J.M., Sharpe, M., Field, D., Soonpaa, M.H., Field, L.J., Burns, C.E., Burns, C.G.
ID
ZDB-PUB-180228-15
Date
2018
Source
Developmental Cell   44: 433-446.e7 (Journal)
Registered Authors
Burns (Erter), Caroline, Burns, Geoff, Gonzalez-Rosa, Juan Manuel
Keywords
cardiomyocyte, cardiomyocyte proliferation, heart regeneration, polyploidization, zebrafish
MeSH Terms
  • Animals
  • Animals, Genetically Modified/embryology
  • Animals, Genetically Modified/physiology*
  • Cell Proliferation
  • Cells, Cultured
  • Heart/embryology*
  • Heart/physiology
  • Myocardial Infarction/metabolism
  • Myocardial Infarction/pathology*
  • Myocardium/cytology*
  • Myocardium/metabolism
  • Polyploidy*
  • Regeneration/physiology*
  • Zebrafish/embryology
  • Zebrafish/physiology*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
29486195 Full text @ Dev. Cell
Abstract
Correlative evidence suggests that polyploidization of heart muscle, which occurs naturally in post-natal mammals, creates a barrier to heart regeneration. Here, we move beyond a correlation by demonstrating that experimental polyploidization of zebrafish cardiomyocytes is sufficient to suppress their proliferative potential during regeneration. Initially, we determined that zebrafish myocardium becomes susceptible to polyploidization upon transient cytokinesis inhibition mediated by dominant-negative Ect2. Using a transgenic strategy, we generated adult animals containing mosaic hearts composed of differentially labeled diploid and polyploid-enriched cardiomyocyte populations. Diploid cardiomyocytes outcompeted their polyploid neighbors in producing regenerated heart muscle. Moreover, hearts composed of equivalent proportions of diploid and polyploid cardiomyocytes failed to regenerate altogether, demonstrating that a critical percentage of diploid cardiomyocytes is required to achieve heart regeneration. Our data identify cardiomyocyte polyploidization as a barrier to heart regeneration and suggest that mobilizing rare diploid cardiomyocytes in the human heart will improve its regenerative capacity.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes