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Title: Nanostring microRNA microarry analysis of p53 and Mdm2 knockout mouse hearts compared to vehicle-injected negative controls      
dateReleased:
03-22-2017
description:
Adult cardiomyocytes (CM) are terminally differentiated cells with minimal regenerative capacity, making cardiac tissue particularly vulnerable to injury. Thus, defining the roadblocks responsible for adult CM cell cycle arrest lies at the core of developing therapies to regenerate myocyte loss following injurious events such as myocardial infarction. We have previously shown that inactivating the p53/Mdm2 tumor suppressor circuitry, specifically in the heart (using the Cre-loxP recombination system of bacteriophage P1), can allow differentiated CMs to regain proliferative capacity, through an upregulation of factors involved in cell cycle re-entry. These factors are repressed in quiescent CMs, in part through the action of microRNAs (miRNAs). Notably, knockout of either p53 or Mdm2 individually was insufficient to promote CM proliferation. Therefore, we hypothesized that inactivation of p53/Mdm2-regulated miRNAs could promote the expression of cell cycle activators and induce proliferation of adult murine CMs. To identify miRNAs regulated by both p53 and Mdm2, total miRNA expression profiles from cardiac specific p53/Mdm2 double knockout (DKO) mouse hearts were compared with those from cardiac-specific single knockouts (p53KO and Mdm2KO), and vehicle-injected controls using the Nanostring nCounter mouse miRNA expression assay. This revealed a profile of 11 significantly downregulated miRNAs in the proliferative DKO hearts (versus vehicle-injected control), that were enriched for mRNA targets involved in cell cycle regulation. In vitro studies have demonstrated that knockdown of these 11 miRNAs in neonatal rat cardiomyocytes can increase the occurrence of cytokinetic events. Ultimately, we aim to inject antagomirs targeting these miRNAs into animals post-myocardial infarction to determine the effect of p53/Mdm2-regulated miRNAs on heart function and CM proliferation in vivo.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-MTAB-5531
refinement:
raw
dateSubmitted:
03-03-2015
keywords:
functional genomics
dateModified:
02-28-2017
creators:
Shanna Stanley-Hasnain
availability:
available
types:
gene expression
name:
Mus musculus
name:
genotype design
ID:
A-GEOD-15089
name:
NanoString nCounter mouse miRNA expression platform
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-MTAB-5531/E-MTAB-5531.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-MTAB-5531/E-MTAB-5531.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress

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