Student or educator? Sign up with your school email and get 6 months of Pro free.
CoChat
Sign Up
Cited by 1,100

The DOI matches its Crossref record; 19 of the 19 references it cites were found in a registry or an index.

SARS ‐CoV‐2 receptor ACE 2 and TMPRSS 2 are primarily expressed in bronchial transient secretory cells

Open access
Lukassen, Soeren, Chua, Robert Lorenz, Trefzer, Timo, Kahn, Nicolas C, Schneider, Marc A, Muley, Thomas, Winter, Hauke, Meister, Michael, Veith, Carmen, Boots, Agnes W, Hennig, Bianca P, Kreuter, Michael, Conrad, Christian, Eils, Roland·2020·The EMBO Journal
DOI 10.15252/embj.20105114

Published version of a preprint

Open this paper in CoChat — free account

Abstract

Abstract The SARS‐CoV‐2 pandemic affecting the human respiratory system severely challenges public health and urgently demands for increasing our understanding of COVID‐19 pathogenesis, especially host factors facilitating virus infection and replication. SARS‐CoV‐2 was reported to enter cells via binding to ACE2, followed by its priming by TMPRSS2. Here, we investigate ACE2 and TMPRSS2 expression levels and their distribution across cell types in lung tissue (twelve donors, 39,778 cells) and in cells derived from subsegmental bronchial branches (four donors, 17,521 cells) by single nuclei and single cell RNA sequencing, respectively. While TMPRSS2 is strongly expressed in both tissues, in the subsegmental bronchial branches ACE2 is predominantly expressed in a transient secretory cell type. Interestingly, these transiently differentiating cells show an enrichment for pathways related to RHO GTPase function and viral processes suggesting increased vulnerability for SARS‐CoV‐2 infection. Our data provide a rich resource for future investigations of COVID‐19 infection and pathogenesis.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.15252/embj.20105114

Cites

19 of 19 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 19 references

Research works printed but not linked: 41

  1. Bi Q, Wu Y, Mei S, Ye C, Zou X, Zhang Z, Liu X, Wei L, Truelove SA, Zhang T et al (2020) Epidemiology and transmission of COVID‐19 in 391 cases and 1286 of their close contacts in Shenzhen, China: a retrospective cohort study. Lancet Infect Dis https://doi.org/10.1016/S1473-3099(20)30287-5 · DOI · Paper page
  2. Brussow H (2020) The novel coronavirus – a snapshot of current knowledge. Microb Biotechnol 13: 607–612 · DOI
  3. Burkard C, Verheije MH, Wicht O, van Kasteren SI, van Kuppeveld FJ, Haagmans BL, Pelkmans L, Rottier PJ, Bosch BJ, de Haan CA (2014) Coronavirus cell entry occurs through the endo‐/lysosomal pathway in a proteolysis‐dependent manner. PLoS Pathog 10: e1004502 · DOI · Paper page
  4. Chan JF, Yuan S, Kok KH, To KK, Chu H, Yang J, Xing F, Liu J, Yip CC, Poon RW et al (2020) A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person‐to‐person transmission: a study of a family cluster. Lancet 395: 514–523 · DOI · Paper page
  5. Coutard B, Valle C, de Lamballerie X, Canard B, Seidah NG, Decroly E (2020) The spike glycoprotein of the new coronavirus 2019‐nCoV contains a furin‐like cleavage site absent in CoV of the same clade. Antiviral Res 176: 104742 · DOI · Paper page
  6. Dumm RE, Fiege JK, Waring BM, Kuo CT, Langlois RA, Heaton NS (2019) Non‐lytic clearance of influenza B virus from infected cells preserves epithelial barrier function. Nat Commun 10: 779 · DOI
  7. Dunn OJ (1964) Multiple comparisons using rank sums. Technometrics 6: 241–252 · DOI · Paper page
  8. Gorbalenya AE, Baker SC, Baric RS, de Groot RJ, Drosten C, Gulyaeva AA, Haagmans BL, Lauber C, Leontovich AM, Neuman BW et al (2020) The species Severe acute respiratory syndrome‐related coronavirus: classifying 2019‐nCoV and naming it SARS‐CoV‐2. Nat Microbiol 5: 536–544 · DOI · Paper page
  9. Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H (2004) Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol 203: 631–637 · DOI · Paper page
  10. Hoffmann M, Kleine‐Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A et al (2020) SARS‐CoV‐2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 181: 271–280 · DOI · Paper page
  11. Jia HP, Look DC, Shi L, Hickey M, Pewe L, Netland J, Farzan M, Wohlford‐Lenane C, Perlman S, McCray PB Jr (2005) ACE2 receptor expression and severe acute respiratory syndrome coronavirus infection depend on differentiation of human airway epithelia. J Virol 79: 14614–14621 · DOI · Paper page
  12. Kahn N, Kuner R, Eberhardt R, Meister M, Muley T, Winteroll S, Schnabel PA, Ishizaka A, Herth FJ, Poustka A et al (2009) Gene expression analysis of endobronchial epithelial lining fluid in the evaluation of indeterminate pulmonary nodules. J Thorac Cardiovasc Surg 138: 474–479 · DOI
  13. Kawase M, Shirato K, van der Hoek L, Taguchi F, Matsuyama S (2012) Simultaneous treatment of human bronchial epithelial cells with serine and cysteine protease inhibitors prevents severe acute respiratory syndrome coronavirus entry. J Virol 86: 6537–6545 · DOI · Paper page
  14. Kido H, Okumura Y, Takahashi E, Pan HY, Wang S, Yao D, Yao M, Chida J, Yano M (2012) Role of host cellular proteases in the pathogenesis of influenza and influenza‐induced multiple organ failure. Biochim Biophys Acta 1824: 186–194 · DOI
  15. Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, Wang W, Song H, Huang B, Zhu N et al (2020) Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 395: 565–574 · DOI · Paper page
  16. Matsuyama S, Ujike M, Morikawa S, Tashiro M, Taguchi F (2005) Protease‐mediated enhancement of severe acute respiratory syndrome coronavirus infection. Proc Natl Acad Sci USA 102: 12543–12547 · DOI · Paper page
  17. Millet JK, Whittaker GR (2014) Host cell entry of Middle East respiratory syndrome coronavirus after two‐step, furin‐mediated activation of the spike protein. Proc Natl Acad Sci USA 111: 15214–15219 · DOI · Paper page
  18. Muley TR, Herth FJ, Schnabel PA, Dienemann H, Meister M (2012) From tissue to molecular phenotyping: pre‐analytical requirements heidelberg experience. Transl Lung Cancer Res 1: 111–121
  19. Qiu X, Mao Q, Tang Y, Wang L, Chawla R, Pliner HA, Trapnell C (2017) Reversed graph embedding resolves complex single‐cell trajectories. Nat Methods 14: 979–982 · DOI · Paper page
  20. Ren X, Glende J, Al‐Falah M, de Vries V, Schwegmann‐Wessels C, Qu X, Tan L, Tschernig T, Deng H, Naim HY et al (2006) Analysis of ACE2 in polarized epithelial cells: surface expression and function as receptor for severe acute respiratory syndrome‐associated coronavirus. J Gen Virol 87: 1691–1695 · DOI
  21. Simmons G, Reeves JD, Rennekamp AJ, Amberg SM, Piefer AJ, Bates P (2004) Characterization of severe acute respiratory syndrome‐associated coronavirus (SARS‐CoV) spike glycoprotein‐mediated viral entry. Proc Natl Acad Sci USA 101: 4240–4245 · DOI · Paper page
  22. Simmons G, Zmora P, Gierer S, Heurich A, Pohlmann S (2013) Proteolytic activation of the SARS‐coronavirus spike protein: cutting enzymes at the cutting edge of antiviral research. Antiviral Res 100: 605–614 · DOI · Paper page
  23. Sims AC, Burkett SE, Yount B, Pickles RJ (2008) SARS‐CoV replication and pathogenesis in an in vitro model of the human conducting airway epithelium. Virus Res 133: 33–44 · DOI
  24. Sungnak W, Huang N, Bécavin C, Berg M, Network HLB (2020) SARS‐CoV‐2 entry genes are most highly expressed in nasal goblet and ciliated cells within human airways. arXiv arXiv:2003.06122 [PREPRINT] · arXiv
  25. Tosti L, Hang Y, Trefzer T, Steiger K, Ten FW, Lukassen S, Ballke S, Kuehl AA, Spieckermann S, Bottino R et al (2019) Single nucleus RNA sequencing maps acinar cell states in a human pancreas cell atlas. bioRxiv https://doi.org/10.1101/733964 [PREPRINT] · DOI
  26. Van den Broeke C, Jacob T, Favoreel HW (2014) Rho'ing in and out of cells: viral interactions with Rho GTPase signaling. Small GTPases 5: e28318 · DOI
  27. Vidricaire G, Denault JB, Leduc R (1993) Characterization of a secreted form of human furin endoprotease. Biochem Biophys Res Commun 195: 1011–1018 · DOI
  28. Walls AC, Tortorici MA, Bosch BJ, Frenz B, Rottier PJM, DiMaio F, Rey FA, Veesler D (2016) Cryo‐electron microscopy structure of a coronavirus spike glycoprotein trimer. Nature 531: 114–117 · DOI · Paper page
  29. Walls AC, Park Y‐J, Tortorici MA, Wall A, McGuire AT, Veesler D (2020) Structure, function and antigenicity of the SARS‐CoV‐2 spike glycoprotein. Cell 180: 281–292 · DOI · Paper page
  30. Wang H, Yang P, Liu K, Guo F, Zhang Y, Zhang G, Jiang C (2008) SARS coronavirus entry into host cells through a novel clathrin‐ and caveolae‐independent endocytic pathway. Cell Res 18: 290–301 · DOI · Paper page
  31. Wang C, Horby PW, Hayden FG, Gao GF (2020a) A novel coronavirus outbreak of global health concern. Lancet 395: 470–473 · DOI · Paper page
  32. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y et al (2020b) Clinical characteristics of 138 hospitalized patients with 2019 novel Coronavirus‐infected pneumonia in Wuhan, China. JAMA 323: 1061–1069 · DOI · Paper page
  33. White JM, Whittaker GR (2016) Fusion of enveloped viruses in endosomes. Traffic 17: 593–614 · DOI · Paper page
  34. Wu Z, McGoogan JM (2020) Characteristics of and important lessons from the coronavirus disease 2019 (COVID‐19) outbreak in China: summary of a Report of 72314 cases from the Chinese Center for disease control and prevention. JAMA 323: 1239–1242 · DOI · Paper page
  35. Wu A, Peng Y, Huang B, Ding X, Wang X, Niu P, Meng J, Zhu Z, Zhang Z, Wang J et al (2020a) Genome composition and divergence of the novel coronavirus (2019‐nCoV) originating in China. Cell Host Microbe 27: 325–328 · DOI · Paper page
  36. Wu C, Yang Y, Liu Y, Zhang P, Wang Y, Wang Q, Xu Y, Li M, Zheng M, Chen L et al (2020b) Furin, a potential therapeutic target for COVID‐19. chinaRxiv https://doi.org/10.12074/202002.00062 [PREPRINT] · DOI
  37. Yan R, Zhang Y, Li Y, Xia L, Guo Y, Zhou Q (2020) Structural basis for the recognition of the SARS‐CoV‐2 by full‐length human ACE2. Science 367: 1444–1448 · DOI · Paper page
  38. Zhang JJ, Dong X, Cao YY, Yuan YD, Yang YB, Yan YQ, Akdis CA, Gao YD (2020a) Clinical characteristics of 140 patients infected with SARS‐CoV‐2 in Wuhan, China. Allergy https://doi.org/10.1111/all.14238 · DOI · Paper page
  39. Zhang Y‐Z, Koopmans M, Yuen KY (2020b) The novel coronavirus outbreak: what we know and what we don't. Cell 180: 1034–1036 · DOI
  40. Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huang CL et al (2020) A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579: 270–273 · DOI · Paper page
  41. Zou X, Chen K, Zou J, Han P, Hao J, Han Z (2020) The single‐cell RNA‐seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to Wuhan 2019‐nCoV infection. Front Med https://doi.org/10.1007/s11684-020-0754-0 · DOI · Paper page

Cited by

See all 1,100

Metadata

Authors
Lukassen, S., Chua, R. L., Trefzer, T., Kahn, N. C., Schneider, M. A., Muley, T., Winter, H., Meister, M., Veith, C., Boots, A. W., Hennig, B. P., Kreuter, M., Conrad, C., & Eils, R.
Venue
The EMBO Journal
Publisher
Springer Science and Business Media LLC
Published
2020-04-14
Volume
39
Issue
10
Pages
e105114-e105114
ISSN
  • 0261-4189 (ISSN-L)
  • 1460-2075
DOI
10.15252/embj.20105114
OpenAlex
W3015134137
Cited by
1,100
References
19
FWCI
29.09
Type
journal article
Language
en
Open access
hybrid
Licence
Funders
Horizon 2020 Framework Programme (874710)

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: SARS ‐CoV‐2 receptor ACE 2 and TMPRSS 2 are primarily expressed in bronchial transient secretory cells. https://app.cochat.ai/papers/10.15252/embj.20105114
The paper
Lukassen, S., Chua, R. L., Trefzer, T., Kahn, N. C., Schneider, M. A., Muley, T., Winter, H., Meister, M., Veith, C., Boots, A. W., Hennig, B. P., Kreuter, M., Conrad, C., & Eils, R. (2020). SARS ‐CoV‐2 receptor ACE 2 and TMPRSS 2 are primarily expressed in bronchial transient secretory cells. The EMBO Journal. https://doi.org/10.15252/embj.20105114

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.