In vivo activation of a conserved microRNA program induces mammalian heart regeneration.

Détails

ID Serval
serval:BIB_750954ED315B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
In vivo activation of a conserved microRNA program induces mammalian heart regeneration.
Périodique
Cell stem cell
Auteur⸱e⸱s
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.
ISSN
1875-9777 (Electronic)
ISSN-L
1875-9777
Statut éditorial
Publié
Date de publication
06/11/2014
Peer-reviewed
Oui
Volume
15
Numéro
5
Pages
589-604
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
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.
Mots-clé
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
Web of science
Open Access
Oui
Création de la notice
14/08/2018 9:36
Dernière modification de la notice
20/08/2019 14:32
Données d'usage