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Cell Stem Cell. 2014 Nov 6;15(5):589-604. doi: 10.1016/j.stem.2014.10.003. Epub 2014 Nov 6.

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

Author information

1
Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
2
Center of Regenerative Medicine of Barcelona (CMRB), 08003 Barcelona, Spain.
3
International Center for Genetic Engineering and Biotechnology (ICGEB), 34149 Trieste, Italy.
4
Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, SR-11, La Jolla, CA 92037, USA.
5
Renal Division, Hospital Clinic, University of Barcelona, IDIBAPS, 08036 Barcelona, Spain.
6
Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA. Electronic address: belmonte@salk.edu.

Erratum in

  • Cell Stem Cell. 2014 Dec 4;15(6):805.

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.

PMID:
25517466
PMCID:
PMC4270016
DOI:
10.1016/j.stem.2014.10.003
[Indexed for MEDLINE]
Free PMC Article

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