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

By Furong Qi, Shen Qian, Shuye Zhang, Zheng Zhang. bioRxiv, 2020

870 citations recorded by the source corpus.

The new coronavirus (2019-nCoV) 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 2019-nCov 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. 2019-nCoV 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.

Subfields: Infectious Diseases, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/2f76444eaf96af0dfae96153c1c22b4f8139e473

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Citations in the corpus

COVID-19: angiotensin-converting enzyme 2 (ACE2) expression and tissue susceptibility to SARS-CoV-2 infection (2021, background): “Alveolar cells (AT1 and AT2) account for 31% of cells in the lungs [23]; however, ACE2 expression is concentrated in a population of AT2 cells that also express viral process-related genes [25].”
SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues (2020, neutral): “During the preparation of this manuscript, several papers have been posted to bioRxiv assessing patterns of ACE2+ and TMPRSS2+ cells in barrier tissues (Brann et al., 2020; Lukassen et al., 2020; Qi et al., 2020; WU et al., 2020; Zhang et al., 2020).”
SARS-CoV-2 productively infects human gut enterocytes (2020, background): “Yet, highest expression of ACE2 in the human body occurs in the brush border of intestinal enterocytes (14, 17).”
Deciphering cell–cell interactions and communication from gene expression (2020, background): “Remarkably, this approach revealed new roles of cells within a tissue 41 and helped explain how ageing 32,47 , diseases 34–36, 48–51 , infections 52 and During the study of CCC, considering spatial context clarifies relationships between cells across tissues and organs.”
Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2 (2020, neutral): “This may be due to the fact that there might be other co-receptors/auxiliary proteins or even other mechanisms by which viruses can enter cells, as had been initially proposed for SARS (Jeffers et al., 2004; Qi et al., 2020) .”