Single-cell Analysis of ACE2 Expression in Human Kidneys and Bladders Reveals a Potential Route of 2019-nCoV Infection

Abstract

Since December 2019, a novel coronavirus named 2019 coronavirus (2019-nCoV) has emerged in Wuhan of China and spread to several countries worldwide within just one month.Apart from fever and respiratory complications, acute kidney injury has been observed in some patients with 2019-nCoV. In a short period of time, angiotensin converting enzyme II (ACE2), have been proposed to serve as the receptor for the entry of 2019-nCoV, which is the same for severe acute respiratory syndrome coronavirus (SARS). To investigate the possible cause of kidney damage in 2019-nCoV patients, we used both published kidney and bladder cell atlas data and an independent unpublished kidney single cell RNA-Seq data generated in-house to evaluate ACE2 gene expressions in all cell types in healthy kidneys and bladders.Our results showed the enriched expression of all subtypes of proximal tubule cells of kidney and low but detectable levels of expression in bladder epithelial cells. These results indicated the urinary system is a potential route for 2019-nCoV infection, along with the respiratory system and digestion system. Our findings suggested the kidney abnormalities of SARS and 2019-nCoV patients may be due to proximal tubule cells damage and subsequent systematic inflammatory response induced kidney injury. Beyond that, laboratory tests of viruses and related indicators in urine may be needed in some special patients of 2019-nCoV.

Potential microenvironment of SARS-CoV-2 infection in airway epithelial cells revealed by Human Protein Atlas database analysis

“…First, ACE2 was found highly expressed in intestine, kidney, gallbladder, adrenal gland, testis, and seminal vesicle among 61 organs in the HPA, at both the protein and RNA levels ( Figure S1), consistenting with previous reports [13,14]. Single-cell sequencing also showed that ACE2 was expressed in only amounts in airway tissue and type II alveolar cells (AT2).…”

“…For example, SARS-CoV mainly binds to cells expressing angiotensin-converting enzyme 2 (ACE2), which is one of the major receptors of SARS-CoV when entering cells [11]. To date, more studies have confirmed that ACE2 is also the receptor of SARS-CoV-2 infection [4]; however, ACE2 displays high expression in the kidney, bile duct, and testis with low expression in the airways and lungs [12][13][14]. Lindskog, et al also emphasized that the expression of ACE2 in human respiratory system is limited, and questioned the role of ACE2 for infection in human lungs [15].…”

The scRNA-seq expression profiling of the receptor ACE2 and the cellular protease TMPRSS2 reveals human organs susceptible to COVID-19 infection

“…In December 2019, a novel pneumonia coronavirus, recently named Coronavirus Disease 2019 (COVID- 19) by World Health Organization (WHO), was first detected in several patients in Wuhan, China.…”

“…[15][16][17] The esophagus, large intestine (ileum and colon), and pancreas were identified as high-risk organs in the digestive system by the following papers. [16][17][18][19] The kidney and bladder as major organs of urinary system were also indicated to be high ACE2-expressed. 17,20,21 Besides, the testes and uterus were manifested to be susceptible organs, implying that the reproductive system was a potential route of viral infection.…”

Systemic analysis of tissue cells potentially vulnerable to SARS-CoV-2 infection by the protein-proofed single-cell RNA profiling of ACE2, TMPRSS2 and Furin proteases

“…Single-cell RNA (scRNA) profiling is a state-of-the-art tool to dissect gene expression at single cell level, therefore was employed to explore the target cells of the SARS-CoV-2. Based on the profiling of ACE2 mRNA expression in different tissues/organs, multiple types of cells were proposed to be potentially targeted by SARS-CoV-2 virus, including the lung alveolar type 2 (AT2) cells [18], nasal epithelial cells [19], esophageal epithelial cells and intestinal enterocytes [20], liver cholangiocytes [21], cardiomyocytes [22], kidney proximal tubule cells [23], spermatogonia and Leydig/sertoli cells in testis [24]. However, unparallel to the many potential targets cells and organs proposed, the COVID-19 patients primarily displayed typical symptoms of inflammation in lung, where only a very small portion of cells (~0.64% of total cells, and ~1.4% of AT2 cells) expressed ACE2 mRNA [18]; meanwhile, the injuries in other organs/tissues, such as kidney and the intestinal track where ACE2 RNA expressed at high levels, seemed to be uncommon [1,25].…”