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Detailed Analyses of the Expression Patterns of Potential Severe Acute Respiratory Syndrome Coronavirus 2 Receptors in the Human Heart Using Single-Nucleus RNA Sequencing
Frontiers in Cardiovascular Medicine ( IF 3.6 ) Pub Date : 2021-11-30 , DOI: 10.3389/fcvm.2021.757362
Jie Ren 1 , Yuze Zhang 1 , Shishi Liu 2 , Xiangjie Li 3 , Xiaogang Sun 1
Affiliation  

Cardiac injury is a common complication of coronavirus disease 2019 (COVID-19), but the exact mechanisms have not been completely elucidated. The virus receptors on subsets of cells are key determinants of susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Due to its high sequence similarity to SARS-CoV, SARS-CoV-2 also utilizes ACE2 as the cell entry receptor. A growing number of studies have indicated that other receptors apart from ACE2 are involved in SARS-CoV-2 infection. This study aimed to elucidate the expression characteristics of SARS-CoV-2 cellular receptors in the heart. We first investigated ACE2 expression in a comprehensive transcriptional landscape of the human heart comprising single-nucleus RNA-seq (snRNA-seq) data for >280,000 cells. Then, the expression distributions of novel SARS-CoV-2 receptors were analyzed at the single-cell level to clarify the cardiovascular complications in COVID-19. We observed a higher percentage of ACE2-positive cells in pericytes (8.3%), fibroblasts (5.1%), and adipocytes (4.4%) in the human heart, compared to other cell types. The frequency of ACE2-positive cells in each cell type from the ventricles was significantly higher than that in the atria, suggesting that the ventricular cells are more susceptible to SARS-CoV-2 infection. The distribution patterns of other receptors (BSG, HSPA5, KREMEN1, NRP1, ANPEP, AXL) were significantly different from those of ACE2, demonstrating higher expression levels in ventricular cardiomyocytes. Moreover, our results suggest that fibroblasts and adipocytes, aside from pericytes, may be vulnerable targets for SARS-CoV-2 infection in the human heart. Our study presents potential targets for future clinical studies and interventions for cardiac injury in patients with COVID-19.



中文翻译:

使用单核 RNA 测序对人心脏中潜在严重急性呼吸综合征冠状病毒 2 受体的表达模式进行详细分析

心脏损伤是 2019 年冠状病毒病 (COVID-19) 的常见并发症,但其确切机制尚未完全阐明。细胞亚群上的病毒受体是严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 感染易感性的关键决定因素。由于其与 SARS-CoV 的序列高度相似,SARS-CoV-2 也利用 ACE2 作为细胞进入受体。越来越多的研究表明,除 ACE2 之外的其他受体也参与了 SARS-CoV-2 感染。本研究旨在阐明SARS-CoV-2细胞受体在心脏中的表达特征。我们首先研究了 ACE2 在人类心脏的综合转录景观中的表达,包括 >280,000 个细胞的单核 RNA-seq (snRNA-seq) 数据。然后,在单细胞水平上分析了新型 SARS-CoV-2 受体的表达分布,以阐明 COVID-19 的心血管并发症。与其他细胞类型相比,我们观察到人类心脏中周细胞 (8.3%)、成纤维细胞 (5.1%) 和脂肪细胞 (4.4%) 中 ACE2 阳性细胞的百分比更高。来自心室的每种细胞类型中 ACE2 阳性细胞的频率显着高于心房中的频率,表明心室细胞更容易受到 SARS-CoV-2 感染。其他受体(BSG、HSPA5、KREMEN1、NRP1、ANPEP、AXL)的分布模式与 ACE2 的分布模式显着不同,表明在心室心肌细胞中表达水平更高。此外,我们的结果表明,除了周细胞外,成纤维细胞和脂肪细胞,可能是人类心脏中 SARS-CoV-2 感染的脆弱目标。我们的研究为 COVID-19 患者心脏损伤的未来临床研究和干预提供了潜在的目标。

更新日期:2021-11-30
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