ScRNA-seq Profiling of Human Testes Reveals the Presence of the ACE2 Receptor, A Target for SARS-CoV-2 Infection in Spermatogonia, Leydig and Sertoli Cells.

Zhengpin Wang,Xiaojiang Xu

doi:10.3390/cells9040920

Abstract

In December 2019, a novel coronavirus (SARS-CoV-2) was identified in COVID-19 patients in Wuhan, Hubei Province, China. SARS-CoV-2 shares both high sequence similarity and the use of the same cell entry receptor, angiotensin-converting enzyme 2 (ACE2), with severe acute respiratory syndrome coronavirus (SARS-CoV). Several studies have provided bioinformatic evidence of potential routes of SARS-CoV-2 infection in respiratory, cardiovascular, digestive and urinary systems. However, whether the reproductive system is a potential target of SARS-CoV-2 infection has not yet been determined. Here, we investigate the expression pattern of ACE2 in adult human testes at the level of single-cell transcriptomes. The results indicate that ACE2 is predominantly enriched in spermatogonia and Leydig and Sertoli cells. Gene Set Enrichment Analysis (GSEA) indicates that Gene Ontology (GO) categories associated with viral reproduction and transmission are highly enriched in ACE2-positive spermatogonia, while male gamete generation related terms are downregulated. Cell–cell junction and immunity-related GO terms are increased in ACE2-positive Leydig and Sertoli cells, but mitochondria and reproduction-related GO terms are decreased. These findings provide evidence that the human testis is a potential target of SARS-CoV-2 infection, which may have significant impact on our understanding of the pathophysiology of this rapidly spreading disease.

Highlights

In December 2019, a novel coronavirus designated SARS-CoV-2 was identified in patients with pneumonia in Wuhan, Hubei Province of China
It has been reported that SARS-CoV-2 shares 76% amino acid sequence identity with severe acute respiratory syndrome coronavirus (SARS-CoV), and is likely to use the same receptor, angiotensin-converting enzyme 2 (ACE2), for entry into target host cells [4,5,6]
We found that ACE2-positive spermatogonia represented 1.28% of all spermatogonia in human testis as shown in Figure 3A, with similar expression level of ACE2-expressing cells (1.40% ± 0.40%) in AT2 cells [6]

Summary

Introduction

In December 2019, a novel coronavirus designated SARS-CoV-2 was identified in patients with pneumonia in Wuhan, Hubei Province of China. The new coronavirus disease has received an official name, coronavirus disease 2019 (COVID-19) from the World Health Organization. It can cause acute respiratory distress syndrome and infected patients have a relatively high risk of death [1,2,3]. It has been reported that SARS-CoV-2 shares 76% amino acid sequence identity with severe acute respiratory syndrome coronavirus (SARS-CoV), and is likely to use the same receptor, angiotensin-converting enzyme 2 (ACE2), for entry into target host cells [4,5,6]. Recent studies provide structural and functional evidence that SARS-CoV-2 entry into cells is recognized by full-length human ACE2 [7,8]. Structural and functional studies have demonstrated that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry

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Results

Conclusion