During heart regeneration, newly proliferated cardiomyocytes redifferentiate and integrate into existing heart tissue. A fundamental question in cardiovascular biology is whether the genetic programs, including cis-regulatory elements (CREs), that drive embryonic heart muscle differentiation are reactivated during adult heart regeneration. Project DC4 investigates these regulatory mechanisms by comparing differentiating cardiomyocytes from developing zebrafish embryos and regenerating adult zebrafish hearts. Moving beyond standard gene expression analysis, our work isolates promoters and explores the transcription factors (TFs) binding to key enhancers to map how regulatory networks operate. Leveraging bulk and single-cell RNA-seq, ATAC-seq, and integrative genomics, we map CRE dynamics and decode transcription factor interactions to construct robust gene regulatory networks in cardiomyocytes. To maximize community impact, DC4 is teaming up with visualization groups of DanoReCode network to integrate these data into innovative, accessible visualization tools for the scientific community. Finally, we will validate the function of regeneration-responsive CREs and enhancers in vivo using transgenic fluorescent reporter lines in developing cardiomyocytes.
