Cited by 912SARS-CoV-2 and COVID-19 ResearchSingle-cell and spatial transcriptomicsCOVID-19 Clinical Research Studies

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

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Qi, Furong, Qian, Shen, Zhang, Shuye, Zhang, Zheng·2020·Biochemical and Biophysical Research Communications

DOI 10.1016/j.bbrc.2020.03.044PMC PMC7156119

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Abstract

The 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.

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Authors: Qi, F., Qian, S., Zhang, S., & Zhang, Z.
Affiliations: Shenzhen Third People’s Hospital (CN)
Shanghai Medical College of Fudan University (CN)
Southern University of Science and Technology (CN)
Corresponding author: Zhang, Shuye
Zhang, Zheng
ORCID: Qi, Furong
Zhang, Shuye
Zhang, Zheng
Venue: Biochemical and Biophysical Research Communications
Publisher: Elsevier BV
Published: 2020-05
Volume: 526
Issue: 1
Pages: 135-140
ISSN: 0006-291X (ISSN-L)
DOI: 10.1016/j.bbrc.2020.03.044
PMC: PMC7156119
OpenAlex: W3011994656
Cited by: 905
References: 40
Citations by year: 2026: 5 · 2025: 28 · 2024: 64 · 2023: 124 · 2022: 155 · 2021: 236 · 2020: 291
FWCI: 26.44
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by-nc-nd/4.0/ (vor)
Locations: Biochemical and Biophysical Research Communications (publishedVersion, cc-by-nc-nd)
bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
Keywords: SARS-CoV-2, ACE2, coronavirus receptor, co-receptors, ANPEP, dipeptidyl peptidase IV, glutamyl aminopeptidase, proteolytic enzymes, intercellular communication, macrophages, chemokine signaling, phagocytosis, human tissue, cell types, single-cell transcriptomics, CellPhoneDB
MeSH terms: Betacoronavirus, Angiotensin-Converting Enzyme 2, COVID-19, SARS-CoV-2, Humans, Peptidyl-Dipeptidase A, Macrophages, Organ Specificity, Peptide Hydrolases, Pneumonia, Viral, Receptors, Virus, Sequence Analysis, RNA, Coronavirus, Coronavirus Infections, Pandemics, Single-Cell Analysis

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

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