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首页> 外文期刊>BMC Genomics >Transcriptome profile of the sinoatrial ring reveals conserved and novel genetic programs of the zebrafish pacemaker
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Transcriptome profile of the sinoatrial ring reveals conserved and novel genetic programs of the zebrafish pacemaker

机译：窦圈的转录组剖面揭示了斑马皮起搏器的保守和新颖的遗传程序

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Sinoatrial 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. To 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. Our 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.
机译：Sinoatrial节点（SAN）是心脏传导系统的一部分，它控制脊椎动物心脏的节奏收缩。 SAN由专业的起搏器细胞群组成，具有产生电脉冲的潜力。虽然San Pacemaker在哺乳动物和Textost模型中被广泛研究，但包括斑马鱼，他们的分子性质仍然不充分理解。为了表征斑马鱼窦环（SAR）的分子曲线并阐明起搏器功能的机制，我们利用转基因线SQET33MI59BET分离开发斑马鱼胚胎的SAR细胞并分析其转录组。我们的分析确定了涉及起搏器发育的新型候选基因和众所周知的保守信号通路。我们表明，与剩下的内心相比，斑马鱼SAR过表达了几种哺乳动物三川王牌签名基因，包括HCN4以及编码钙和钾门通道的那些。此外，在SAR中，编码BMP和WNT信号传导途径的组分的基因以及先前涉及的TBX系列的成员在SAR中也过度表达。在SAR过度表达基因中，24种具有与各种形式的先天性心脏病有关的104种不同的Clinvar表型条目的人类同源物，这表明我们的转录组织资源与研究人体状况的相关性。最后，三种SAR过表达基因，PARD6A，PROM2和ATP1A1A.2的功能分析发现了它们在心脏发育和生理学中的新作用。我们的成果在斑马鱼和哺乳动物起搏器功能之间建立了保守的方面，并揭示了涉及维持心律的新因素。本研究中产生的转录组数据是对起搏器功能和相关心脏病研究的独特和有价值的资源。

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