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The copyright holder for this preprint (which was not peer-reviewed) is the .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 protein expression of ACE2, TMPRSS2 and Furin in situ from IHC images. Tissues highly expressing ACE2 either at mRNA level or protein level were included for analysis, in addition, the putative SARS-CoV-2 target tissues proposed by previous researches irrespective of ACE2 expression level were also included. This resulted in a list of 15 tissues in total ( Figure 2 and S2), which, based on the IHC intensity of ACE2, could be roughly categorised into 3 groups. The ACE2-high group contains kidney, stomach, small intestine, colon, gallbladder and testis. In this group of tissues, ACE2 was generally expressed at the apical region, facing the luminal surface, of epithelial cells ( Figure 2D -E, S2B-D), which means that efficient host entry of virus could only take place from the luminal side. This rule may not be applied to testis as high level of ACE2 expression was also detected in the stromal cells ( Figure 2F ), which are not polarized and could be potentially accessed by virus from the blood stream. The ACE2-low group contains liver, esophagus, breast and adipose tissue, which are unlikely the direct targets of SARS-CoV-2 virus even though some of them showed high levels of mRNA expression, such as breast ( Figure S2E ) and adipose tissues ( Figure S2F ). There is a small amount of ACE2-positive cells in the interlobular region of liver tissue ( Figure 2C ), probably the cholanggiocytes as suggested below in scRNA analysis ( Figure 4C ). These cells might be potential SARS-CoV-2 targets under the condition that viruses come from the luminal side, which is normally rare, as the ACE2 protein was detected at the cell apical surface. The ACE2-median group contains lung, heart, ovary, adrenal gland and thyroid gland. For lung, the major target of SARS-CoV-2 virus, there are considerable amount of ACE2-positive cells in alveolus lumen, which morphologically resemble macrophages and represent for the majority of ACE2-positive cells in the lung tissue ( Figure 2A ). All of the cardiomyocytes, and a portion of stromal cells in ovary, adrenal gland and thyroid gland express ACE2 very well ( Figure 2B , 2G-H, S2G), therefore are potential virus targets in the presence of viremia.