Transcriptome profile of the sinoatrial ring reveals conserved and novel genetic programs of the zebrafish pacemaker

BMC Genomics

Henry Loeffler-Wirth¹  Hans Binder¹  Alexandra Paterek²  Angelika Brzozowska²  Tomasz Obrębski²  Cecilia Lanny Winata²  Shikha Vashisht²  Vladimir Korzh²  Karim Abu Nahia²  Rashid Minhas³  Yusra H. Siddiqui⁴  Katarzyna Piwocka⁵  Lukasz Bugajski⁵ 

[1] Interdisciplinary Centre for Bioinformatics, University of Leipzig, Leipzig, Germany;International Institute of Molecular and Cell Biology in Warsaw, Warsaw, Poland;International Institute of Molecular and Cell Biology in Warsaw, Warsaw, Poland;Randall Centre of Cell and Molecular Biophysics, Faculty of Life Sciences and Medicine, King’s College London, London, UK;International Institute of Molecular and Cell Biology in Warsaw, Warsaw, Poland;School of Human Sciences, College of Science and Engineering, University of Derby, Derby, UK;Nencki Institute of Experimental Biology, Laboratory of Cytometry, Warsaw, Poland;

关键词: Zebrafish;    Cardiac conduction system;    Pacemaker;    Sinoatrial node;    Sinoatrial ring;    RNA-seq;   

DOI  :  10.1186/s12864-021-08016-z

来源: Springer

【 摘 要 】

BackgroundSinoatrial Node (SAN) is part of the cardiac conduction system, which controls the rhythmic contraction of the vertebrate heart. The SAN consists of a specialized pacemaker cell population that has the potential to generate electrical impulses. Although the SAN pacemaker has been extensively studied in mammalian and teleost models, including the zebrafish, their molecular nature remains inadequately comprehended.ResultsTo characterize the molecular profile of the zebrafish sinoatrial ring (SAR) and elucidate the mechanism of pacemaker function, we utilized the transgenic line sqet33mi59BEt to isolate cells of the SAR of developing zebrafish embryos and profiled their transcriptome. Our analyses identified novel candidate genes and well-known conserved signaling pathways involved in pacemaker development. We show that, compared to the rest of the heart, the zebrafish SAR overexpresses several mammalian SAN pacemaker signature genes, which include hcn4 as well as those encoding 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, which suggest the relevance of our transcriptomics resource to studying human heart conditions. Finally, functional analyses of three SAR-overexpressed genes, pard6a, prom2, and atp1a1a.2, uncovered their novel role in heart development and physiology.ConclusionOur results established conserved aspects between zebrafish and mammalian pacemaker function and revealed novel factors implicated in maintaining cardiac rhythm. The transcriptome data generated in this study represents a unique and valuable resource for the study of pacemaker function and associated heart diseases.

【 授权许可】

CC BY