Reciprocal analyses in zebrafish and medaka reveal that harnessing the immune response promotes cardiac regeneration

Shih Lei Lai*, Rubén Marín-Juez, Pedro Luís Moura, Carsten Kuenne, Jason Kuan Han Lai, Ayele Taddese Tsedeke, Stefan Guenther, Mario Looso, Didier Y.R. Stainier

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

115 Citations (Scopus)
400 Downloads (Pure)

Abstract

Zebrafish display a distinct ability to regenerate their heart following injury. However, this ability is not shared by another teleost, the medaka. In order to identify cellular and molecular bases for this difference, we performed comparative transcriptomic analyses following cardiac cryoinjury. This comparison points to major differences in immune cell dynamics between these models. Upon closer examination, we observed delayed and reduced macrophage recruitment in medaka, along with delayed neutrophil clearance. To investigate the role of immune responses in cardiac regeneration, we delayed macrophage recruitment in zebrafish and observed compromised neovascularization, neutrophil clearance, cardiomyocyte proliferation and scar resolution. In contrast, stimulating Toll-like receptor signaling in medaka enhanced immune cell dynamics and promoted neovascularization, neutrophil clearance, cardiomyocyte proliferation and scar resolution. 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.

Original languageEnglish
Article numbere25605
JournaleLife
Volume6
DOIs
Publication statusPublished - 20 Jun 2017

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