PUBLICATION

Comparative transcriptome profiling of the injured zebrafish and mouse hearts identifies miRNA-dependent repair pathways

Authors
Crippa, S., Nemir, M., Ounzain, S., Ibberson, M., Berthonneche, C., Sarre, A., Boisset, G., Maison, D., Harshman, K., Xenarios, I., Diviani, D., Schorderet, D., Pedrazzini, T.
ID
ZDB-PUB-160210-3
Date
2016
Source
Cardiovascular research   110(1): 73-84 (Journal)
Registered Authors
Boisset, Gaƫlle, Schorderet, Daniel
Keywords
Mouse, Myocardial infarction, Repair mechanisms, Zebrafish, miRNAs
Datasets
GEO:GSE51014, GEO:GSE51013, GEO:GSE51018
MeSH Terms
  • Animals
  • Cell Cycle
  • Cell Proliferation/genetics*
  • Gene Expression Profiling/methods
  • Gene Regulatory Networks/genetics*
  • Mice, Inbred C57BL
  • MicroRNAs/genetics
  • MicroRNAs/metabolism*
  • Myocytes, Cardiac/physiology
  • Regeneration
  • Wound Healing/genetics*
  • Zebrafish
PubMed
26857418 Full text @ Cardiovasc. Res.
Abstract
The adult mammalian heart has poor regenerative capacity. In contrast, the zebrafish heart retains a robust capacity for regeneration into adulthood. These distinct responses are consequences of a differential utilization of evolutionary conserved gene regulatory networks in the damaged heart. To systematically identify miRNA-dependent networks controlling cardiac repair following injury, we performed comparative gene and miRNA profiling of the cardiac transcriptome in adult mice and zebrafish.
Using an integrated approach, we show that 45 miRNA-dependent networks, involved in critical biological pathways, are differentially modulated in the injured zebrafish vs. mouse heart. We study more particularly the miR-26a-dependent response. Therefore, miR-26a is downregulated in the fish heart after injury whereas its expression remains constant in the mouse heart. Targets of miR-26a involve activators of the cell cycle and Ezh2, a component of the Polycomb Repressive Complex 2 (PRC2). Importantly, PRC2 exerts repressive functions on negative regulators of the cell cycle. In cultured neonatal cardiomyocytes, inhibition of miR-26a stimulates therefore cardiomyocyte proliferation. Accordingly, miR-26a knockdown prolongs the proliferative window of cardiomyocytes in the post-natal mouse heart.
This novel strategy identifies a series of miRNAs and associated pathways, in particular miR-26a, which represent attractive therapeutic targets for inducing repair in the injured heart.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping