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
-
- Zebrafish
- Myocardium/enzymology
- Tissue Culture Techniques
- Regeneration*
- Telomerase/physiology*
- Myocytes, Cardiac/physiology
- Heart/physiology*
- Zebrafish Proteins/physiology*
- Gene Knockout Techniques
- Animals
- Gene Expression
- Cell Proliferation
- PubMed
- 26321646 Full text @ Cell Rep.
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.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping