Regulatory profiling of the innate immune response during cardiac regeneration
- 1 June 2014 to 31 May 2015
- Awards: Pump-priming Awards
Efforts to restore lost tissue after a heart attack have paid little attention to the local environment of pro-inflammation and ensuing fibrosis. In the neonatal mouse, which regenerates its injured heart during the first week of life, immune cells are indispensable for the regenerative process. This suggests a tight modulation of the immune response may dictate the regeneration of adult heart tissue. We performed a comprehensive transcriptomics analysis of macrophages during adult zebrafish heart regeneration, directly comparing two injury models, scar-inducing cryoinjury and scar-free resection. By employing biotagging of nuclei and RNA-Seq, we revealed active molecular programmes underpinning macrophages ability to initiate, maintain and resolve pro-inflammatory and anti-inflammatory responses to the distinct post-injury environments, which in-turn dictate the kinetics of scar resolution and regeneration. We provided evidence for how a scar-inducing environment can change the phenotype and function of macrophages, eliciting responses that can be finely tuned towards successful regeneration.