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Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection

Frontiers of Medicine volume 14, pages185–192(2020)Cite this article

Abstract

It has been known that, the novel coronavirus, 2019-nCoV, which is considered similar to SARS-CoV, invades human cells via the receptor angiotensin converting enzyme II (ACE2). Moreover, lung cells that have ACE2 expression may be the main target cells during 2019-nCoV infection. However, some patients also exhibit non-respiratory symptoms, such as kidney failure, implying that 2019-nCoV could also invade other organs. To construct a risk map of different human organs, we analyzed the single-cell RNA sequencing (scRNA-seq) datasets derived from major human physiological systems, including the respiratory, cardiovascular, digestive, and urinary systems. Through scRNA-seq data analyses, we identified the organs at risk, such as lung, heart, esophagus, kidney, bladder, and ileum, and located specific cell types (i.e., type II alveolar cells (AT2), myocardial cells, proximal tubule cells of the kidney, ileum and esophagus epithelial cells, and bladder urothelial cells), which are vulnerable to 2019-nCoV infection. Based on the findings, we constructed a risk map indicating the vulnerability of different organs to 2019-nCoV infection. This study may provide potential clues for further investigation of the pathogenesis and route of 2019-nCoV infection.

References

  1. 1.

    WHO. Statement on the second meeting of the International Health Regulations (2005) Emergency Committee regarding the outbreak of novel coronavirus (2019-nCoV). 2020. https://www.who.int/news-room/detail/30-01-2020-statement-on-the-second-meeting-of-the-international-health-regulations-(2005)-emergency-committee-regarding-the-outbreak-of-novel-coronavirus-(2019-ncov) (accessed Janaury 30, 2020)

  2. 2.

    Xu X, Chen P, Wang J, Feng J, Zhou H, Li X, Zhong W, Hao P. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. Sci China Life Sci 2020 Jan 21. [Epub ahead of print] doi: https://doi.org/10.1007/s11427-020-1637-5

    PubMed  PubMed Central  Google Scholar 

  3. 3.

    Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huang CL, Chen HD, Chen J, Luo Y, Guo H, Jiang RD, Liu MQ, Chen Y, Shen XR, Wang X, Zheng XS, Zhao K, Chen QJ, Deng F, Liu LL, Yan B, Zhan FX, Wang YY, Xiao GF, Shi ZL. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020 Feb 3. [Epub ahead of print] doi: https://doi.org/10.1038/s41586-020-2012-7

    CAS  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Reyfman PA, Walter JM, Joshi N, Anekalla KR, McQuattie-Pimentel AC, Chiu S, Fernandez R, Akbarpour M, Chen CI, Ren Z, Verma R, Abdala-Valencia H, Nam K, Chi M, Han S, Gonzalez-Gonzalez FJ, Soberanes S, Watanabe S, Williams KJN, Flozak AS, Nicholson TT, Morgan VK, Winter DR, Hinchcliff M, Hrusch CL, Guzy RD, Bonham CA, Sperling AI, Bag R, Hamanaka RB, Mutlu GM, Yeldandi AV, Marshall SA, Shilatifard A, Amaral LAN, Perlman H, Sznajder JI, Argento AC, Gillespie CT, Dematte J, Jain M, Singer BD, Ridge KM, Lam AP, Bharat A, Bhorade SM, Gottardi CJ, Budinger GRS, Misharin AV. Single-cell transcriptomic analysis of human lung provides insights into the pathobiology of pulmonary fibrosis. Am J Respir Crit Care Med 2019; 199(12): 1517–1536

    CAS  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Ruiz García S, Deprez M, Lebrigand K, Cavard A, Paquet A, Arguel MJ, Magnone V, Truchi M, Caballero I, Leroy S, Marquette CH, Marcet B, Barbry P, Zaragosi LE. Novel dynamics of human mucociliary differentiation revealed by single-cell RNA sequencing of nasal epithelial cultures. Development 2019; 146(20): 146

    Google Scholar 

  6. 6.

    Cui Y, Zheng Y, Liu X, Yan L, Fan X, Yong J, Hu Y, Dong J, Li Q, Wu X, Gao S, Li J, Wen L, Qiao J, Tang F. Single-cell transcriptome analysis maps the developmental track of the human heart. Cell Rep 2019; 26(7): 1934–1950.e5

    CAS  PubMed  Google Scholar 

  7. 7.

    Madissoon E, Wilbrey-Clark A, Miragaia RJ, Saeb-Parsy K, Mahbubani KT, Georgakopoulos N, Harding P, Polanski K, Huang N, Nowicki-Osuch K, Fitzgerald RC, Loudon KW, Ferdinand JR, Clatworthy MR, Tsingene A, van Dongen S, Dabrowska M, Patel M, Stubbington MJT, Teichmann SA, Stegle O, Meyer KB. scRNA-seq assessment of the human lung, spleen, and esophagus tissue stability after cold preservation. Genome Biol 2020; 21(1): 1

    CAS  Google Scholar 

  8. 8.

    Zhang P, Yang M, Zhang Y, Xiao S, Lai X, Tan A, Du S, Li S. Dissecting the single-cell transcriptome network underlying gastric premalignant lesions and early gastric cancer. Cell Rep 2019; 27(6): 1934–1947.e5

    CAS  PubMed  Google Scholar 

  9. 9.

    MacParland SA, Liu JC, Ma XZ, Innes BT, Bartczak AM, Gage BK, Manuel J, Khuu N, Echeverri J, Linares I, Gupta R, Cheng ML, Liu LY, Camat D, Chung SW, Seliga RK, Shao Z, Lee E, Ogawa S, Ogawa M, Wilson MD, Fish JE, Selzner M, Ghanekar A, Grant D, Greig P, Sapisochin G, Selzner N, Winegarden N, Adeyi O, Keller G, Bader GD, McGilvray ID. Single cell RNA sequencing of human liver reveals distinct intrahepatic macrophage populations. Nat Commun 2018; 9(1): 4383

    PubMed  PubMed Central  Google Scholar 

  10. 10.

    Martin JC, Chang C, Boschetti G, Ungaro R, Giri M, Grout JA, Gettler K, Chuang LS, Nayar S, Greenstein AJ, Dubinsky M, Walker L, Leader A, Fine JS, Whitehurst CE, Mbow ML, Kugathasan S, Denson LA, Hyams JS, Friedman JR, Desai PT, Ko HM, Laface I, Akturk G, Schadt EE, Salmon H, Gnjatic S, Rahman AH, Merad M, Cho JH, Kenigsberg E. Single-cell analysis of Crohn’s disease lesions identifies a pathogenic cellular module associated with resistance to anti-TNF therapy. Cell 2019; 178(6): 1493–1508.e20

    CAS  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Wu H, Malone AF, Donnelly EL, Kirita Y, Uchimura K, Ramakrishnan SM, Gaut JP, Humphreys BD. Single-cell transcriptomics of a human kidney allograft biopsy specimen defines a diverse inflammatory response. J Am Soc Nephrol 2018; 29(8): 2069–2080

    CAS  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Yu Z, Liao J, Chen Y, Zou C, Zhang H, Cheng J, Liu D, Li T, Zhang Q, Li J, Yang X, Ye Y, Huang Z, Long X, Yang R, Mo Z. Single-cell transcriptomic map of the human and mouse bladders. J Am Soc Nephrol 2019; 30(11): 2159–2176

    PubMed  Google Scholar 

  13. 13.

    Becht E, McInnes L, Healy J, Dutertre CA, Kwok IWH, Ng LG, Ginhoux F, Newell EW. Dimensionality reduction for visualizing single-cell data using UMAP. Nat Biotechnol 2019; 37: 38–44

    CAS  Google Scholar 

  14. 14.

    Hamming I, Timens W, Bulthuis MLC, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol 2004; 203(2): 631–637

    CAS  PubMed  PubMed Central  Google Scholar 

  15. 15.

    Crackower MA, Sarao R, Oudit GY, Yagil C, Kozieradzki I, Scanga SE, Oliveira-dos-Santos AJ, da Costa J, Zhang L, Pei Y, Scholey J, Ferrario CM, Manoukian AS, Chappell MC, Backx PH, Yagil Y, Penninger JM. Angiotensin-converting enzyme 2 is an essential regulator of heart function. Nature 2002; 417(6891): 822–828

    CAS  PubMed  Google Scholar 

  16. 16.

    Kowalczuk S, Bröer A, Tietze N, Vanslambrouck JM, Rasko JEJ, Bröer S. A protein complex in the brush-border membrane explains a Hartnup disorder allele. FASEB J 2008; 22(8): 2880–2887

    CAS  PubMed  Google Scholar 

  17. 17.

    Donoghue M, Hsieh F, Baronas E, Godbout K, Gosselin M, Stagliano N, Donovan M, Woolf B, Robison K, Jeyaseelan R, Breitbart RE, Acton S. A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1–9. Circ Res 2000; 87(5): E1–E9

    CAS  PubMed  Google Scholar 

  18. 18.

    Harmer D, Gilbert M, Borman R, Clark KL. Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme. FEBS Lett 2002; 532(1–2): 107–110

    CAS  PubMed  Google Scholar 

  19. 19.

    Burrell LM, Risvanis J, Kubota E, Dean RG, MacDonald PS, Lu S, Tikellis C, Grant SL, Lew RA, Smith AI, Cooper ME, Johnston CI. Myocardial infarction increases ACE2 expression in rat and humans. Eur Heart J 2005; 26(4): 369–375, discussion 322–324

    CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported in part by the China National Science and Technology Major Project for Prevention and Treatment of Infectious Diseases (No. 2017ZX10203207 to Z.-G. H.), National Natural Science Foundation of China (No. 81672772 to Z.-G. H., No. 31601070 to J. H., No. 31800253 to K. C.), Interdisciplinary Program of Shanghai Jiao Tong University (Nos. 2019TPA09 and ZH2018ZDA33 to Z.-G. H., J. H., and X. Z.), Shanghai Sailing Program (No. 17YF1410400 to K. C.) and Innovative Research Team of High-Level Local Universities in Shanghai.

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Affiliations

  1. Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Centre for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, China

    Xin Zou, Ke Chen, Jiawei Zou, Jie Hao & Zeguang Han

  2. Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China

    Peiyi Han

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  1. Xin Zou
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  2. Ke Chen
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  3. Jiawei Zou
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Correspondence to Jie Hao or Zeguang Han.

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Xin Zou, Ke Chen, Jiawei Zou, Peiyi Han, Jie Hao, and Zeguang Han declare that they have no conflict of interest. This manuscript does not involve a research protocol requiring approval by the relevant institutional review board or ethics committee.

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The authors wish it to be known that, in their opinion, the first three authors should be regarded as Joint First Authors.

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Zou, X., Chen, K., Zou, J. et al. Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front. Med. 14, 185–192 (2020). https://doi.org/10.1007/s11684-020-0754-0

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Keywords

  • 2019-nCoV
  • ACE2
  • single-cell RNA-seq