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

Considering that mRNA level does not always dictate comparable protein expression, and subcellular localizations, which are missing information from mRNA profiling, are critical for protein functions, we set out to explore ACE2 expression at both mRNA and protein levels by taking advantages of the curated public database. We called this method as protein-proofed scRNA (pscRNA) profiling. Moreover, we also analysed the coexpression of ACE2 with its two processing proteases, TMPRSS2 and Furin, at single cell resolution in situ by pscRNA profiling. Systemic analysis of 36 human tissues/organs revealed that 1) a rank list of potential SARS-CoV-2 targets with lung AT2 cell and macrophages as the top targets, then cardiomyocytes, and stromal cells in testis, ovary, adrenal and thyroid glands. Among them, the lung macrophages, stromal cells in ovary and adrenal gland, were identified for the first time, which may account for severe clinical symptoms and rapid disease progression; 2) the mRNA levels may differ dramatically from the protein levels for ACE2, TMPRSS2 and Furin in different tissue cells; and protein subcellular localization is another factor potentially affecting virus host-entry; 3) the co-expression of ACE2 with TMPRSS2 and Furin proteases may contribute to establish efficient infection of SARS-CoV-2 virus.