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

Lulin Zhou; Zubiao Niu; Xiaoyi Jiang; Zhengrong Zhang; You Zheng; Zhongyi Wang; Yichao Zhu; Lihua Gao; Xiaoning Wang; Qiang Sun

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] . This obvious discrepancy suggests that mechanisms other than ACE2 mRNA levels are also involved in the regulation of SARS-CoV-2 infection of their target cells.