Odz4 upregulates SAN-specific genes to promote differentiation into cardiac pacemaker-like cells.

IF 3.5 4区 生物学 Q1 Biochemistry, Genetics and Molecular Biology FEBS Letters Pub Date : 2024-10-27 DOI:10.1002/1873-3468.15036
Anqi Dong, Masao Yoshizumi, Hiroki Kokubo
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Abstract

Cardiac arrhythmias stemming from abnormal sinoatrial node (SAN) function can lead to sudden death. Developing a biological pacemaker device for treating sick sinus syndrome (SSS) could offer a potential cure. Understanding SAN differentiation is crucial, yet its regulatory mechanism remains unclear. We reanalyzed published RNA-seq data and identified Odz4 as a SAN-specific candidate. In situ hybridization revealed Odz4 expression in the cardiac crescent and throughout the cardiac conduction system (CCS). To assess the role of Odz4 in CCS differentiation, we utilized a Tet-Off inducible system for its intracellular domain (ICD). Embryonic bodies (EBs) exogenously expressing Odz4-ICD exhibited an increased propensity to develop into pacemaker-like cells with enhanced automaticity and upregulated expression of SAN-specific genes. CellChat and GO analyses unveiled SAN-specific enrichment of ligand-receptor sets, especially Ptn-Ncl, and extracellular matrix components in the group exogenously expressing Odz4-ICD. Our findings underscore the significance of Odz4 in SAN development and offer fresh insights into biological pacemaker establishment.

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Odz4上调SAN特异性基因,促进心脏起搏器样细胞的分化。
心房结(SAN)功能异常引起的心律失常可导致猝死。开发用于治疗病态窦房结综合征(SSS)的生物起搏器装置有可能提供一种治疗方法。了解 SAN 的分化至关重要,但其调控机制仍不清楚。我们重新分析了已发表的RNA-seq数据,发现Odz4是SAN特异性候选基因。原位杂交显示 Odz4 在心脏新月和整个心脏传导系统(CCS)中都有表达。为了评估Odz4在CCS分化中的作用,我们使用了一个Tet-Off诱导系统来诱导其胞内结构域(ICD)。外源表达Odz4-ICD的胚胎体(EBs)表现出更强的倾向性,能发育成起搏器样细胞,自动性增强,SAN特异性基因表达上调。CellChat和GO分析揭示了外源表达Odz4-ICD组中配体受体集(尤其是Ptn-Ncl)和细胞外基质成分的SAN特异性富集。我们的研究结果强调了Odz4在SAN发育中的重要性,并为生物起搏器的建立提供了新的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
FEBS Letters
FEBS Letters 生物-生化与分子生物学
CiteScore
7.00
自引率
2.90%
发文量
303
审稿时长
1.0 months
期刊介绍: FEBS Letters is one of the world''s leading journals in molecular biology and is renowned both for its quality of content and speed of production. Bringing together the most important developments in the molecular biosciences, FEBS Letters provides an international forum for Minireviews, Research Letters and Hypotheses that merit urgent publication.
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