PUBLICATION
Transcriptional response to cardiac injury in the zebrafish: systematic identification of genes with highly concordant activity across in vivo models
- Authors
- Rodius, S., Nazarov, P.V., Nepomuceno-Chamorro, I.A., Jeanty, C., González-Rosa, J.M., Ibberson, M., da Costa, R.M., Xenarios, I., Mercader, N., Azuaje, F.
- ID
- ZDB-PUB-141005-10
- Date
- 2014
- Source
- BMC Genomics 15: 852 (Journal)
- Registered Authors
- Mercader Huber, Nadia
- Keywords
- none
- MeSH Terms
-
- Animals
- Computational Biology
- Cytochrome P-450 Enzyme System/genetics
- Cytochrome P-450 Enzyme System/metabolism
- Disease Models, Animal
- Endopeptidases/genetics
- Endopeptidases/metabolism
- Heart/physiology
- Heart Injuries/genetics
- Heart Injuries/metabolism*
- Heart Injuries/pathology
- Myocardium/metabolism
- Myocardium/pathology
- Oligonucleotide Array Sequence Analysis
- Real-Time Polymerase Chain Reaction
- Regeneration
- Time Factors
- Transcriptome
- Tumor Suppressor Protein p53/genetics
- Tumor Suppressor Protein p53/metabolism
- Zebrafish
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 25280539 Full text @ BMC Genomics
Citation
Rodius, S., Nazarov, P.V., Nepomuceno-Chamorro, I.A., Jeanty, C., González-Rosa, J.M., Ibberson, M., da Costa, R.M., Xenarios, I., Mercader, N., Azuaje, F. (2014) Transcriptional response to cardiac injury in the zebrafish: systematic identification of genes with highly concordant activity across in vivo models. BMC Genomics. 15:852.
Abstract
Background 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping