Detailed Analyses of the Expression Patterns of Potential Severe Acute Respiratory Syndrome Coronavirus 2 Receptors in the Human Heart Using Single-Nucleus RNA Sequencing

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...

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Autores principales:	Jie Ren, Yuze Zhang, Shishi Liu, Xiangjie Li, Xiaogang Sun
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	SARS-CoV-2 cardiac injury cellular receptors ACE2 expression features Diseases of the circulatory (Cardiovascular) system RC666-701
Acceso en línea:	https://doaj.org/article/0afc088bbe1c485992451baec89afd34
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spelling	oai:doaj.org-article:0afc088bbe1c485992451baec89afd342021-12-01T16:14:05ZDetailed Analyses of the Expression Patterns of Potential Severe Acute Respiratory Syndrome Coronavirus 2 Receptors in the Human Heart Using Single-Nucleus RNA Sequencing2297-055X10.3389/fcvm.2021.757362https://doaj.org/article/0afc088bbe1c485992451baec89afd342021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcvm.2021.757362/fullhttps://doaj.org/toc/2297-055XCardiac 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.Jie RenYuze ZhangShishi LiuXiangjie LiXiaogang SunFrontiers Media S.A.articleSARS-CoV-2cardiac injurycellular receptorsACE2expression featuresDiseases of the circulatory (Cardiovascular) systemRC666-701ENFrontiers in Cardiovascular Medicine, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	SARS-CoV-2 cardiac injury cellular receptors ACE2 expression features Diseases of the circulatory (Cardiovascular) system RC666-701
spellingShingle	SARS-CoV-2 cardiac injury cellular receptors ACE2 expression features Diseases of the circulatory (Cardiovascular) system RC666-701 Jie Ren Yuze Zhang Shishi Liu Xiangjie Li Xiaogang Sun Detailed Analyses of the Expression Patterns of Potential Severe Acute Respiratory Syndrome Coronavirus 2 Receptors in the Human Heart Using Single-Nucleus RNA Sequencing
description	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.
format	article
author	Jie Ren Yuze Zhang Shishi Liu Xiangjie Li Xiaogang Sun
author_facet	Jie Ren Yuze Zhang Shishi Liu Xiangjie Li Xiaogang Sun
author_sort	Jie Ren
title	Detailed Analyses of the Expression Patterns of Potential Severe Acute Respiratory Syndrome Coronavirus 2 Receptors in the Human Heart Using Single-Nucleus RNA Sequencing
title_short	Detailed Analyses of the Expression Patterns of Potential Severe Acute Respiratory Syndrome Coronavirus 2 Receptors in the Human Heart Using Single-Nucleus RNA Sequencing
title_full	Detailed Analyses of the Expression Patterns of Potential Severe Acute Respiratory Syndrome Coronavirus 2 Receptors in the Human Heart Using Single-Nucleus RNA Sequencing
title_fullStr	Detailed Analyses of the Expression Patterns of Potential Severe Acute Respiratory Syndrome Coronavirus 2 Receptors in the Human Heart Using Single-Nucleus RNA Sequencing
title_full_unstemmed	Detailed Analyses of the Expression Patterns of Potential Severe Acute Respiratory Syndrome Coronavirus 2 Receptors in the Human Heart Using Single-Nucleus RNA Sequencing
title_sort	detailed analyses of the expression patterns of potential severe acute respiratory syndrome coronavirus 2 receptors in the human heart using single-nucleus rna sequencing
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/0afc088bbe1c485992451baec89afd34
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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

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