Single-cell RNA sequencing analysis of human kidney reveals the presence of ACE2 receptor: A potential pathway of COVID-19 infection

Abstract

Background: A novel coronavirus called SARS-Cov-2, which shared 82% similarity of genome sequence with SARS-CoV, was found in Wuhan in late December of 2019, causing an epidemic outbreak of novel coronavirus-induced pneumonia with dramatically increasing number of cases. Several organs are vulnerable to COVID-19 infection. Acute kidney injury (AKI) was reported in parts of case-studies reporting characteristics of COVID-19 patients. This study aimed at analyzing the potential route of SARS-Cov-2 entry and mechanism at cellular level. Method: Single-cell RNA sequencing (scRNA-seq) technology was used to obtain evidence of potential route and ACE2 expressing cell in renal system for underlying pathogenesis of kidney injury caused by COVID-19. The whole process was performed under R with Seurat packages. Canonical marker genes were used to annotate different types of cells. Results: Ten different clusters were identified and ACE2 was mainly expressed in proximal tubule and glomerular parietal epithelial cells. From Gene Ontology (GO) & KEGG enrichment analysis, imbalance of ACE2 expression, renin-angiotensin system (RAS) activation, and neutrophil-related processes were the main issue of COVID-19 leading kidney injury. Conclusion: Our study provided the cellular evidence that SARS-Cov-2 invaded human kidney tissue via proximal convoluted tubule, proximal tubule, proximal straight tubule cells, and glomerular parietal cells by means of ACE2-related pathway and used their cellular protease TMPRSS2 for priming.