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Transcriptome profile of the zebrafish sinoatrial ring

ABSTRACT: Sino Atrial Node (SAN) is part of the cardiac conduction system, which controls the rhythmic contraction of the vertebrate heart. SAN consists of a specialized pacemaker cell population that has the potential to generate electrical impulses. Although SAN pacemakers have been extensively studied in mammalian and teleost models, including the zebrafish, their molecular nature remains inadequately comprehended. Here, we utilized the zebrafish transgenic line sqet33mi59BEt to isolate cells of the sino-atrial ring (SAR) of developing zebrafish embryos and profiled their transcriptome. Our analyses identified novel candidate genes and well-known conserved signaling pathways (Wnt, BMP) involved in pacemaker development. We show that the zebrafish SAR expresses several mammalian SAN pacemaker signature genes, which include hcn4 and calcium and potassium gated channels. Moreover, genes encoding components of the BMP and Wnt signaling pathways, as well as members of the Tbx family, which have previously been implicated in pacemaker development, were also overexpressed in the SAR. Among SAR-overexpressed genes, 24 had human homologues implicated in 104 different ClinVar phenotype entries related to various forms of congenital heart diseases. Moreover, we show that loss-of-function of three SAR-overexpressed genes, pard6a, prom2, and atp1a1a.2, resulted in abnormal heart morphology and physiology. Our results suggest the relevance of our transcriptomics resource to studying human heart conditions.

ORGANISM(S): Danio rerio

PROVIDER: GSE160398 | GEO | 2021/09/10

REPOSITORIES: GEO

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