Reactivation of an Embryonic Cardiac Neural Crest Transcriptional Subcircuit During Zebrafish Heart Regeneration [bulk RNA-seq]

During vertebrate development, the heart primarily arises from mesoderm, with crucial contributions from cardiac neural crest cells that migrate to the heart and form a variety of cardiovascular derivatives. Here, by integrating bulk and single cell RNAseq with ATAC-seq, we identify a gene regulatory subcircuit specific to migratory cardiac crest cells composed of key transcription factors egr1, sox9a, tfap2a and ets1. Notably, we show that cells expressing the canonical neural crest gene sox10 are essential for proper cardiac regeneration in adult zebrafish. Furthermore, expression of all transcription factors from the migratory cardiac crest gene subcircuit are reactivated after injury at the wound edge. Together, our results uncover a developmental gene regulatory network that is important for cardiac neural crest fate determination, with key factors re-activated during regeneration. Overall design: Migratory cardiac neural crest cells (mcherry +) and non-neural crest cells from the same tissue (mcherry -) were FAC-sorted from 16 somite-stage Tg(-4.9sox10:GAL4-UAS-cre;UAS:NfsB-mCherry;myl7:nucGFP) embryos. Migratory trunk neural crest cells (GFP +) were FAC-sorted from 24hpf Tg(-4.9sox10:eGFP) embryos.