Related Experiment Video
Updated: Dec 25, 2025
Author Spotlight: Deciphering the Cellular Mysteries of Intermuscular Adipose Tissue in Humans
Published on: May 3, 2024
Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses
Furong Qi1, Shen Qian1, Shuye Zhang2
1Institute of Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Shenzhen, Guangdong Province, 518100, China.
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.
Insights
Researchers identified potential co-receptors for SARS-CoV-2, the virus causing COVID-19. Peptidases like ANPEP, DPP4, and ENPEP show similar expression patterns to ACE2, suggesting they may aid viral entry and are key targets for understanding coronavirus infections.
Area of Science:
- Virology
- Genomics
- Immunology
Background:
- The novel coronavirus (SARS-CoV-2) outbreak has become a global health emergency.
- Angiotensin-converting enzyme 2 (ACE2) is the primary receptor for SARS-CoV-2 entry into human cells, but its expression is low in some tissues like the lungs.
- SARS-CoV-2 may utilize co-receptors to enhance viral entry.
Purpose of the Study:
- To identify potential co-receptors that facilitate SARS-CoV-2 entry by analyzing single-cell gene expression data.
- To investigate the co-expression patterns of known viral receptors and other membrane proteins with ACE2 across various human tissues.
- To explore cell-cell communication involving SARS-CoV-2 target cells and surrounding immune cells.
Main Methods:
- Analysis of a single-cell gene expression atlas comprising 119 cell types from 13 human tissues.
- Examination of co-expression spectra for 51 RNA virus receptors and 400 membrane proteins.
- Utilizing CellPhoneDB for analyzing cell crosstalk between virus target cells and other tissue cells.
Main Results:
- ACE2 expression was confirmed in specific cell types across lung, liver, colon, esophagus, ileum, rectum, stomach, and kidney.
- Peptidases ANPEP, DPP4, and ENPEP exhibited expression patterns highly similar to ACE2 across the analyzed tissues.
- ANPEP and DPP4 are known receptors for human coronaviruses, identifying ENPEP as a potential novel receptor.
- Macrophages engage in significant crosstalk with virus target cells via chemokine and phagocytosis signaling.
Conclusions:
- ANPEP, DPP4, and ENPEP are identified as potential co-receptors for SARS-CoV-2, with ENPEP being a novel candidate.
- The findings highlight the role of these peptidases in facilitating coronavirus entry.
- Tissue macrophages play a crucial role in the immune response and pathogenesis of coronavirus infections through intercellular communication.
