Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses

Abstract

a b s t r a c tThe new coronavirus (SARS-CoV-2) outbreak from December 2019 in Wuhan, Hubei, China, has been declared a global public health emergency. Angiotensin I converting enzyme 2 (ACE2), is the host receptor by SARS-CoV-2 to infect human cells. Although ACE2 is reported to be expressed in lung, liver, stomach, ileum, kidney and colon, its expressing levels are rather low, especially in the lung. SARS-CoV-2 may use co-receptors/auxiliary proteins as ACE2 partner to facilitate the virus entry. To identify the potential candidates, we explored the single cell gene expression atlas including 119 cell types of 13 human tissues and analyzed the single cell co-expression spectrum of 51 reported RNA virus receptors and 400 other membrane proteins. Consistent with other recent reports, we confirmed that ACE2 was mainly expressed in lung AT2, liver cholangiocyte, colon colonocytes, esophagus keratinocytes, ileum ECs, rectum ECs, stomach epithelial cells, and kidney proximal tubules. Intriguingly, we found that the candidate co-receptors, manifesting the most similar expression patterns with ACE2 across 13 human tissues, are all peptidases, including ANPEP, DPP4 and ENPEP. Among them, ANPEP and DPP4 are the known receptors for human CoVs, suggesting ENPEP as another potential receptor for human CoVs. We also conducted "CellPhoneDB" analysis to understand the cell crosstalk between CoV-targets and their surrounding cells across different tissues. We found that macrophages frequently communicate with the CoVs targets through chemokine and phagocytosis signaling, highlighting the importance of tissue macrophages in immune defense and immune pathogenesis.

Virus strain of a mild COVID-19 patient in Hangzhou represents a new trend in SARS-CoV-2 evolution related to Furin cleavage site

“…7E). Consistently with previously report 31 , ACE2 was mainly expressed in alveolar type 2 cells in lung ( Fig. 7D-E).…”

“…Among ZJ01 unique mutations, 10 (NO. [22][23][24][25][26][27][28][29][30][31] were located on the S protein, including 3 samesense mutation, 2 deletion mutation and 5 missense mutation, which led to amino acid changes of Ser596, Gln613, Glu702, Ala771, Ala1015, Pro1053 and Thr1066. Further similarity analysis indicated that the main difference among various coronaviruses located in the Receptor Binding Domain (RBD) region of S1.…”

Critical role of type III interferon in controlling SARS-CoV-2 infection, replication and spread in primary human intestinal epithelial cells

“…S4A-E). This is very different to the small intestine where ACE-2 appears to be more expressed (Qi et al, 2020). This low ACE-2 level could explain why we have a small percentage of infected cells in our colon organoids (Fig.…”

Integrated analyses of single-cell atlases reveal age, gender, and smoking status associations with cell type-specific expression of mediators of SARS-CoV-2 viral entry and highlights inflammatory programs in putative target cells

“…Specifically, nasal goblet cells and multiciliated cells comprised the highest fraction of dualpositive ACE2 + TMPRSS2 + cells 45 , consistent with a plausible role for a nasal viral reservoir that supports transmissivity. In the distal lung, co-expression occurred in AT2 cells 45,47,48 . Previous surveys across other tissues also showed a relatively high portion of ACE2 + TMPRSS2 + cells within colonic enterocytes, another potential viral reservoir that promotes viral transmission 49 .…”