Comparative transcriptome profiling of zebrafish and medaka hearts following cardiac cryoinjury

Heart failure results from the inability of the human heart to replenish damaged tissue after myocardial infarction (MI), forming an unresolved scar which leads to functional impairment and tissue remodeling. Unlike humans, many animals, including certain fish and amphibians, are able to regenerate their hearts. Comparative analyses have been performed in many model systems including zebrafish (Danio rerio), with the goal to identify factors that could promote cardiac regeneration in humans. However, profound physiological differences between regenerative and non-regenerative models often make it difficult to extract informative data that are directly relevant to cardiac regeneration. Recently, medaka (Oryzias latipes), another fresh water teleost, has been reported to lack activation of neovascularization and cardiomyocyte (CM) proliferation post cardiac injury, and to display excessive fibrosis and an unresolved scar. This finding constitutes a unique opportunity to directly compare reparative responses to cardiac injury between regenerative (zebrafish) and non-regenerative (medaka) models with common physiological condition and anatomical structures, as well as phylogenetically close orthologous genes. Here we investigate potential triggers that promote heart regeneration using a comparative transcriptomic analysis between zebrafish and medaka. We generated a detailed dataset containing more than 15000 orthologous genes, covering multiple time points in the first week after cardiac injury. Analyses based on gene ontology revealed that differential responses in processes such as the immune response and angiogenesis exist between the two models. Pathway analyses further suggested potential candidates accounting for these differential responses including the Toll-like receptor agonist poly I:C. Altogether, these data provide further insight into the complex role of the immune response during regeneration, and serve as a platform to identify and test additional regulators of cardiac repair.