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dc.contributor.authorRodius, Sophieen_US
dc.contributor.authorNazarov, Petr Ven_US
dc.contributor.authorNepomuceno-Chamorro, Isabel Aen_US
dc.contributor.authorJeanty, Célineen_US
dc.contributor.authorGonzález-Rosa, Juan Manuelen_US
dc.contributor.authorIbberson, Marken_US
dc.contributor.authorda Costa, Ricardo M Benitesen_US
dc.contributor.authorXenarios, Ioannisen_US
dc.contributor.authorMercader, Nadiaen_US
dc.contributor.authorAzuaje, Franciscoen_US
dc.date.accessioned2014-11-03T17:39:52Z
dc.date.issued2014en_US
dc.identifier.citationRodius, Sophie, Petr V Nazarov, Isabel A Nepomuceno-Chamorro, Céline Jeanty, Juan Manuel González-Rosa, Mark Ibberson, Ricardo M Benites da Costa, Ioannis Xenarios, Nadia Mercader, and Francisco Azuaje. 2014. “Transcriptional response to cardiac injury in the zebrafish: systematic identification of genes with highly concordant activity across in vivo models.” BMC Genomics 15 (1): 852. doi:10.1186/1471-2164-15-852. http://dx.doi.org/10.1186/1471-2164-15-852.en
dc.identifier.issn1471-2164en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:13347553
dc.description.abstractBackground: Zebrafish is a clinically-relevant model of heart regeneration. Unlike mammals, it has a remarkable heart repair capacity after injury, and promises novel translational applications. Amputation and cryoinjury models are key research tools for understanding injury response and regeneration in vivo. An understanding of the transcriptional responses following injury is needed to identify key players of heart tissue repair, as well as potential targets for boosting this property in humans. Results: We investigated amputation and cryoinjury in vivo models of heart damage in the zebrafish through unbiased, integrative analyses of independent molecular datasets. To detect genes with potential biological roles, we derived computational prediction models with microarray data from heart amputation experiments. We focused on a top-ranked set of genes highly activated in the early post-injury stage, whose activity was further verified in independent microarray datasets. Next, we performed independent validations of expression responses with qPCR in a cryoinjury model. Across in vivo models, the top candidates showed highly concordant responses at 1 and 3 days post-injury, which highlights the predictive power of our analysis strategies and the possible biological relevance of these genes. Top candidates are significantly involved in cell fate specification and differentiation, and include heart failure markers such as periostin, as well as potential new targets for heart regeneration. For example, ptgis and ca2 were overexpressed, while usp2a, a regulator of the p53 pathway, was down-regulated in our in vivo models. Interestingly, a high activity of ptgis and ca2 has been previously observed in failing hearts from rats and humans. Conclusions: We identified genes with potential critical roles in the response to cardiac damage in the zebrafish. Their transcriptional activities are reproducible in different in vivo models of cardiac injury. Electronic supplementary material The online version of this article (doi:10.1186/1471-2164-15-852) contains supplementary material, which is available to authorized users.en
dc.language.isoen_USen
dc.publisherBioMed Centralen
dc.relation.isversionofdoi:10.1186/1471-2164-15-852en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4197235/pdf/en
dash.licenseLAAen_US
dc.subjectMyocardial infarctionen
dc.subjectZebrafishen
dc.subjectVentricular amputationen
dc.subjectVentricular cryoinjuryen
dc.subjectHeart regenerationen
dc.subjectTranscriptional responsesen
dc.subjectTranscriptional association networksen
dc.titleTranscriptional response to cardiac injury in the zebrafish: systematic identification of genes with highly concordant activity across in vivo modelsen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalBMC Genomicsen
dc.date.available2014-11-03T17:39:52Z
dc.identifier.doi10.1186/1471-2164-15-852*


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