PUBLICATION
In Vivo Activation of a Conserved MicroRNA Program Induces Mammalian Heart Regeneration
- Authors
- Aguirre, A., Montserrat, N., Zacchigna, S., Nivet, E., Hishida, T., Krause, M.N., Kurian, L., Ocampo, A., Vazquez-Ferrer, E., Rodriguez-Esteban, C., Kumar, S., Moresco, J.J., Yates, J.R., Campistol, J.M., Sancho-Martinez, I., Giacca, M., Izpisua Belmonte, J.C.
- ID
- ZDB-PUB-141218-3
- Date
- 2014
- Source
- Cell Stem Cell 15: 589-604 (Journal)
- Registered Authors
- Keywords
- none
- Datasets
- GEO:GSE62386, GEO:GSE62389
- MeSH Terms
-
- Animals
- Cell Dedifferentiation/genetics
- Cell Proliferation
- Down-Regulation/genetics
- Gene Expression Regulation, Developmental*
- Gene Silencing
- Genome
- Heart/physiology*
- Humans
- Mammals/genetics*
- Mice, Inbred C57BL
- MicroRNAs/genetics*
- MicroRNAs/metabolism
- Myocardium/metabolism
- Myocytes, Cardiac/cytology
- Myocytes, Cardiac/metabolism
- Regeneration/genetics*
- Zebrafish/genetics
- PubMed
- 25517466 Full text @ Cell Stem Cell
Citation
Aguirre, A., Montserrat, N., Zacchigna, S., Nivet, E., Hishida, T., Krause, M.N., Kurian, L., Ocampo, A., Vazquez-Ferrer, E., Rodriguez-Esteban, C., Kumar, S., Moresco, J.J., Yates, J.R., Campistol, J.M., Sancho-Martinez, I., Giacca, M., Izpisua Belmonte, J.C. (2014) In Vivo Activation of a Conserved MicroRNA Program Induces Mammalian Heart Regeneration. Cell Stem Cell. 15:589-604.
Abstract
Heart failure is a leading cause of mortality and morbidity in the developed world, partly because mammals lack the ability to regenerate heart tissue. Whether this is due to evolutionary loss of regenerative mechanisms present in other organisms or to an inability to activate such mechanisms is currently unclear. Here we decipher mechanisms underlying heart regeneration in adult zebrafish and show that the molecular regulators of this response are conserved in mammals. We identified miR-99/100 and Let-7a/c and their protein targets smarca5 and fntb as critical regulators of cardiomyocyte dedifferentiation and heart regeneration in zebrafish. Although human and murine adult cardiomyocytes fail to elicit an endogenous regenerative response after myocardial infarction, we show that in vivo manipulation of this molecular machinery in mice results in cardiomyocyte dedifferentiation and improved heart functionality after injury. These data provide a proof of concept for identifying and activating conserved molecular programs to regenerate the damaged heart.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping