PUBLICATION

Telomerase Is Essential for Zebrafish Heart Regeneration

Authors
Bednarek, D., González-Rosa, J.M., Guzmán-Martínez, G., Gutiérrez-Gutiérrez, Ó., Aguado, T., Sánchez-Ferrer, C., Marques, I.J., Galardi-Castilla, M., de Diego, I., Gómez, M.J., Cortés, A., Zapata, A., Jiménez-Borreguero, L.J., Mercader, N., Flores, I.
ID
ZDB-PUB-150901-6
Date
2015
Source
Cell Reports   12(10): 1691-703 (Journal)
Registered Authors
Marques, Ines, Mercader Huber, Nadia
Keywords
none
Datasets
GEO:GSE71755
MeSH Terms
  • Regeneration*
  • Myocardium/enzymology
  • Zebrafish Proteins/physiology*
  • Myocytes, Cardiac/physiology
  • Gene Knockout Techniques
  • Cell Proliferation
  • Animals
  • Zebrafish
  • Heart/physiology*
  • Telomerase/physiology*
  • Gene Expression
  • Tissue Culture Techniques
(all 12)
PubMed
26321646 Full text @ Cell Rep.
Abstract
After myocardial infarction in humans, lost cardiomyocytes are replaced by an irreversible fibrotic scar. In contrast, zebrafish hearts efficiently regenerate after injury. Complete regeneration of the zebrafish heart is driven by the strong proliferation response of its cardiomyocytes to injury. Here we show that, after cardiac injury in zebrafish, telomerase becomes hyperactivated, and telomeres elongate transiently, preceding a peak of cardiomyocyte proliferation and full organ recovery. Using a telomerase-mutant zebrafish model, we found that telomerase loss drastically decreases cardiomyocyte proliferation and fibrotic tissue regression after cryoinjury and that cardiac function does not recover. The impaired cardiomyocyte proliferation response is accompanied by the absence of cardiomyocytes with long telomeres and an increased proportion of cardiomyocytes showing DNA damage and senescence characteristics. These findings demonstrate the importance of telomerase function in heart regeneration and highlight the potential of telomerase therapy as a means of stimulating cell proliferation upon myocardial infarction.
Genes / Markers
Figures
Figure Gallery (13 images) / 2
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Expression
No data available
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
hu3430
    		Point Mutation
    twu34TgTransgenic Insertion
      y1TgTransgenic Insertion
        1 - 3 of 3
        Show
        Human Disease / Model
        No data available
        Sequence Targeting Reagents
        Target Reagent Reagent Type
        tertMO1-tertMRPHLNO
        1 - 1 of 1
        Show
        Fish
        No data available
        Antibodies
        Orthology
        No data available
        Engineered Foreign Genes
        Marker Marker Type Name
        EGFPEFGEGFP
        1 - 1 of 1
        Show
        Mapping
        No data available
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        Citation
        Bednarek, D., González-Rosa, J.M., Guzmán-Martínez, G., Gutiérrez-Gutiérrez, Ó., Aguado, T., Sánchez-Ferrer, C., Marques, I.J., Galardi-Castilla, M., de Diego, I., Gómez, M.J., Cortés, A., Zapata, A., Jiménez-Borreguero, L.J., Mercader, N., Flores, I. (2015) Telomerase Is Essential for Zebrafish Heart Regeneration. Cell Reports. 12(10):1691-703.