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Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses
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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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“ACE2 expression has been reported for many tissues/organs including the lung (ie, lung type II alveolar cells/AT2, bronchial epithelial cells), brain, kidney, small intestine, colon, and heart.”
From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [9]
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“TMPRSS2 is also required for SARS-CoV and Middle Eastern respiratory syndrome coronavirus viral entry.”
From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [9]
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Metadata
- 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
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2020-05
- Volume
- 526
- Issue
- 1
- Pages
- 135-140
- ISSN
- 0006-291X (ISSN-L)
- 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
- 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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