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

The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.06.028522 doi: bioRxiv preprint injury [1, 25] , and a rate of 3.5%-5.8% for intestinal symptoms [1, 47] . Instead, the injuries in ACE2-median organs such as heart are more frequent (12%-19%) [1, 47] . This obvious discrepancy suggests that mechanisms other than ACE2 expression level also play important roles in establishing efficient and successful infection. Based on our above analysis by pscRNA expression profiling, we propose that three more factors, in addition to the mRNA level, should be taken into account in predicting the vulnerability of a specified target tissue/organ. First, the protein information of expression level, subcellular localization may influence virus infection. As shown above, the mRNA level is not often corresponding to protein level, such as in kidney and adipose tissue (Figure 1) , therefore, it's necessary to not only analyse mRNA expression, but also detect protein expression in situ. Moreover, membrane proteins such as ACE2 could be expressed either all around the surface of nonpolarized stromal cells such as Leydig cells in testis ( Figure 2F and 3F) , or specifically on the apical region of polarized epithelial cells such as the enterocytes in intestinal tracts ( Figure 2E ). This means much for virus infection as it determines how the viruses may get access to their target cells and enter. For the polarized cells, virus could only successfully infect cells from the luminal side, where ACE2 is expressed on apical surface but not the basal-lateral surfaces. While for the non-polarized stromal cells, virus may readily come to see them from the blood stream.