|
| Status |
Public on Nov 20, 2014 |
| Title |
In vivo activation of a conserved microRNA program induces robust mammalian heart regeneration (array) |
| Platform organism |
synthetic construct |
| Sample organism |
Danio rerio |
| Experiment type |
Non-coding RNA profiling by array
|
| Summary |
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 following 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.
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| |
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| Overall design |
Analysis of miRNA levels in regenerating zebrafish hearts
|
| |
|
| Contributor(s) |
Aguirre A, Belmonte JC |
| Citation(s) |
25517466 |
| |
| Submission date |
Oct 15, 2014 |
| Last update date |
May 02, 2017 |
| Contact name |
Christopher Benner |
| E-mail(s) |
cbenner@ucsd.edu
|
| Organization name |
University of California, San Diego (UCSD)
|
| Department |
Medicine
|
| Street address |
9500 Gilman Dr. MC 0640
|
| City |
La Jolla |
| State/province |
California |
| ZIP/Postal code |
92093-0640 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL14613 |
[miRNA-2] Affymetrix Multispecies miRNA-2 Array |
|
| Samples (5)
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| This SubSeries is part of SuperSeries: |
| GSE62389 |
In vivo activation of a conserved microRNA program induces robust mammalian heart regeneration |
|
| Relations |
| BioProject |
PRJNA263965 |
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