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Frontiers of Medicine

Front. Med.    2020, Vol. 14 Issue (2) : 185-192     https://doi.org/10.1007/s11684-020-0754-0
RESEARCH ARTICLE
Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection
Xin Zou1, Ke Chen1, Jiawei Zou1, Peiyi Han2, Jie Hao1(), Zeguang Han1()
1. Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Centre for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China
2. Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
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Abstract

It has been known that, the novel coronavirus, 2019-nCoV, which is considered similar to SARS-CoV, invades human cells via the receptor angiotensin converting enzyme II (ACE2). Moreover, lung cells that have ACE2 expression may be the main target cells during 2019-nCoV infection. However, some patients also exhibit non-respiratory symptoms, such as kidney failure, implying that 2019-nCoV could also invade other organs. To construct a risk map of different human organs, we analyzed the single-cell RNA sequencing (scRNA-seq) datasets derived from major human physiological systems, including the respiratory, cardiovascular, digestive, and urinary systems. Through scRNA-seq data analyses, we identified the organs at risk, such as lung, heart, esophagus, kidney, bladder, and ileum, and located specific cell types (i.e., type II alveolar cells (AT2), myocardial cells, proximal tubule cells of the kidney, ileum and esophagus epithelial cells, and bladder urothelial cells), which are vulnerable to 2019-nCoV infection. Based on the findings, we constructed a risk map indicating the vulnerability of different organs to 2019-nCoV infection. This study may provide potential clues for further investigation of the pathogenesis and route of 2019-nCoV infection.

Keywords 2019-nCoV      ACE2      single-cell RNA-seq     
Corresponding Authors: Jie Hao,Zeguang Han   
Just Accepted Date: 08 February 2020   Online First Date: 13 March 2020    Issue Date: 09 May 2020
 Cite this article:   
Xin Zou,Ke Chen,Jiawei Zou, et al. Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection[J]. Front. Med., 2020, 14(2): 185-192.
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http://journal.hep.com.cn/fmd/EN/10.1007/s11684-020-0754-0
http://journal.hep.com.cn/fmd/EN/Y2020/V14/I2/185
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Xin Zou
Ke Chen
Jiawei Zou
Peiyi Han
Jie Hao
Zeguang Han
Fig.1  Respiratory track scRNA-seq data analysis showed epithelial cells with high ACE2 expression levels. (A) The cells were categorized into five clusters. (B) Violin plot of the ACE2 expression distribution of different cell clusters. (C) Scatter plots revealed that the cluster of cells with ACE2 expression also expressed canonical markers of respiratory epithelial cells PIGR and MUC1.
Fig.2  Heart scRNA-seq data analysis revealed myocardial cells with high ACE2 expression levels. (A) The cells were categorized into 10 clusters. (B) Violin plot of the ACE2 expression distribution of different cell clusters. (C) Scatter plots of the cluster of cells with high ACE2 expression levels also expressed canonical markers of myocardial cells MYL3 and MYH7.
Fig.3  ScRNA-seq data analysis showed that ileal epithelial cells have high ACE2 expression. (A) The cells were categorized into nine clusters. (B) Violin plot of the ACE2 expression distribution of different cell clusters. (C) Scatter plots showed that the cluster of cells with high ACE2 expression also expressed canonical markers of ileal epithelial cells, FABP6, and ANPEP.
Fig.4  Esophagus scRNA-seq data analysis revealed that a few esophageal epithelial cells express ACE2. (A) The cells were categorized into 18 cell types. (B) Violin plot of the ACE2 expression distribution of different cell clusters. (C) ACE2 expression distribution demonstrated in a scatter plot.
Fig.5  Kidney scRNA-seq data analysis revealed that the proximal tubule (PT) cells highly express ACE2. (A) The cells were categorized into 14 clusters. (B) Violin plot of the ACE2 expression distribution of different cell clusters. (C) Scatter plots showed that the cluster of cells with high ACE2 expression also expressed canonical markers of kidney proximal tubule cells CUBN and LRP2.
Fig.6  Bladder scRNA-seq data analysis showed that a few cells express ACE2. (A) The cells were categorized into six clusters. (B) Violin plot of the ACE2 expression distribution of different cell clusters. (C) Scatter plots showed that the cluster of cells with high ACE2 expression also expressed canonical markers of bladder urothelial cells CLDN4 and SPINK1.
Fig.7  2019-nCoV infection-related vulnerable organs with high risk are highlighted in red; low-risk organs are indicated in gray.
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