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Digestive system is a potential route of COVID-19: an analysis of single-cell coexpression pattern of key proteins in viral entry process
  1. Hao Zhang1,2,3,
  2. Zijian Kang1,3,
  3. Haiyi Gong2,3,
  4. Da Xu3,4,
  5. Jing Wang5,
  6. Zhixiu Li6,
  7. Zifu Li5,
  8. Xinggang Cui4,
  9. Jianru Xiao2,
  10. Jian Zhan7,
  11. Tong Meng3,8,9,
  12. Wang Zhou3,10,
  13. Jianmin Liu5,
  14. Huji Xu1,10,11
  1. 1 Department of Rheumatology and Immunology, Changzheng Hospital, Second Military Medical University, Shanghai, China
  2. 2 Department of Orthopaedic Oncology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China
  3. 3 Qiu-Jiang Bioinformatics Institute, Shanghai, China
  4. 4 Department of Urology, The Third Affiliated Hospital of Second Military Medical University, Shanghai, China
  5. 5 Department of Neurosurgery, Changhai Hospital, Second Military Medical University, Shanghai, China
  6. 6 Translational Genomics Group, Institute of Health and Biomedical Innovation, Queensland University of Technology, Translational Research Institute, Brisbane, Queensland, Australia
  7. 7 Institute for Glycomics, Griffith University, Southport, QLD, Australia
  8. 8 Division of Spine, Department of Orthopedics, Tongji Hospital affiliated to Tongji University School of Medicine, Shanghai, China
  9. 9 Tongji University Cancer Center, School of Medicine, Tongji University, Shanghai, China
  10. 10 Peking-Tsinghua Center for Life Sciences, Tsinghua University, Beijing, China
  11. 11 Beijing Tsinghua Changgeng Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
  1. Correspondence to Professor Huji Xu, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China; xuhuji{at}smmu.edu.cn; Professor Jianmin Liu, Changhai Hospital, Second Military Medical University, Shanghai, China; chstroke{at}163.com; Dr Wang Zhou, Peking-Tsinghua Center for Life Sciences, Tsinghua University, Beijing, China; brilliant212{at}163.com; Dr Tong Meng, Tongji Hospital affiliated to Tongji University School of Medicine, Shanghai, China; mengtong{at}medmail.com.cn; Dr Jian Zhan, Institute for Glycomics, Griffith University, Southport, QLD, Australia; j.zhan{at}griffith.edu.au

Abstract

Objective Since December 2019, a newly identified coronavirus (severe acute respiratory syndrome coronavirus (SARS-CoV-2)) has caused outbreaks of pneumonia in Wuhan, China. SARS-CoV-2 enters host cells via cell receptor ACE II (ACE2) and the transmembrane serine protease 2 (TMPRSS2). In order to identify possible prime target cells of SARS-CoV-2 by comprehensive dissection of ACE2 and TMPRSS2 coexpression pattern in different cell types, five datasets with single-cell transcriptomes of lung, oesophagus, gastric mucosa, ileum and colon were analysed.

Design Five datasets were searched, separately integrated and analysed. Violin plot was used to show the distribution of differentially expressed genes for different clusters. The ACE2-expressing and TMPRRSS2-expressing cells were highlighted and dissected to characterise the composition and proportion.

Results Cell types in each dataset were identified by known markers. ACE2 and TMPRSS2 were not only coexpressed in lung AT2 cells and oesophageal upper epithelial and gland cells but also highly expressed in absorptive enterocytes from the ileum and colon. Additionally, among all the coexpressing cells in the normal digestive system and lung, the expression of ACE2 was relatively highly expressed in the ileum and colon.

Conclusion This study provides the evidence of the potential route of SARS-CoV-2 in the digestive system along with the respiratory tract based on single-cell transcriptomic analysis. This finding may have a significant impact on health policy setting regarding the prevention of SARS-CoV-2 infection. Our study also demonstrates a novel method to identify the prime cell types of a virus by the coexpression pattern analysis of single-cell sequencing data.

  • infectious disease
  • receptor binding
  • medical decision analysis
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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Footnotes

  • HZ, ZK, HG and DX are joint first authors.

  • JZ, TM, WZ, JL and HX are joint senior authors.

  • HZ, ZK, HG and DX contributed equally.

  • JZ, TM, WZ, JL and HX contributed equally.

  • Contributors WZ and HZ: study design. HZ, WZ, HG and DX: data analysis. ZL, ZK, HG and DX: data collection and generation. JZ, JW, ZL, XC and JX: data interpretation. TM, ZK and HX: manuscript drafting. JZ, TM, WZ, JL and HX: overall supervising and organising the study.

  • Funding HX was supported by the National Natural Science Foundation of China (Grant 31821003) and the China Ministry of Science and Technology (Grant 2018AAA0100300).

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Patient consent for publication Not required.

  • Ethics approval There is no direct involvement of human subjects in this project. All the data use existing deidentified biological samples and data from prior studies. Therefore, ethical oversight and patient consent were not handled in this study.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Single cell data can be obtained in Human Cell Atalas accession code PRJEB31843 (https://data.humancellatlas.org/explore/projects/c4077b3c-5c98-4d26-a614-246d12c2e5d7),Gene Expression Omnibus(GSE134520 and GSE134809) and Single Cell Portal accession code SCP259(https://singlecell.broadinstitute.org/single_cell/study/SCP259/intra-and-inter-cellular-rewiring-of-the-human-colon-during-ulcerative-colitis). All data relevant to the study are descripted in detail in the article or uploaded as supplementary information.

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