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, Gaëlle, Schorderet, Daniel
Keywords
Mouse, Myocardial infarction, Repair mechanisms, Zebrafish, miRNAs
Datasets
GEO:GSE51014, GEO:GSE51018, GEO:GSE51013
MeSH Terms
  • Gene Regulatory Networks/genetics*
  • Myocytes, Cardiac/physiology
  • Wound Healing/genetics*
  • Gene Expression Profiling/methods
  • Cell Cycle
  • MicroRNAs/genetics
  • MicroRNAs/metabolism*
  • Animals
  • Regeneration
  • Mice, Inbred C57BL
  • Zebrafish
  • Cell Proliferation/genetics*
(all 12)
PubMed
26857418 Full text @ Cardiovasc. Res.
Abstract
Aim 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.
Methods and results 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.
Conclusions 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
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Expression
Phenotype
No data available
Mutations / Transgenics
No data available
Human Disease / Model
No data available
Sequence Targeting Reagents
Fish
No data available
Antibodies
No data available
Orthology
No data available
Engineered Foreign Genes
No data available
Mapping
No data available
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Citation
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. (2016) Comparative transcriptome profiling of the injured zebrafish and mouse hearts identifies miRNA-dependent repair pathways. Cardiovascular research. 110(1):73-84.