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Cited by 348

The DOI matches its Crossref record; 25 of the 25 references it cites were found in a registry or an index.

Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics

Open access
Muus, Christoph, Luecken, Malte D., Eraslan, Gökcen, Sikkema, Lisa, Waghray, Avinash, Heimberg, Graham, Kobayashi, Yoshihiko, Vaishnav, Eeshit Dhaval, Subramanian, Ayshwarya, Smillie, Christopher, Jagadeesh, Karthik A., Duong, Elizabeth Thu, Fiskin, Evgenij, Torlai Triglia, Elena, Ansari, Meshal, Cai, Peiwen, Lin, Brian, Buchanan, Justin, Chen, Sijia, Shu, Jian, Haber, Adam L., Chung, Hattie, Montoro, Daniel T., Adams, Taylor, Aliee, Hananeh, Allon, Samuel J., Andrusivova, Zaneta, Angelidis, Ilias, Ashenberg, Orr, Bassler, Kevin, Bécavin, Christophe, Benhar, Inbal, Bergenstråhle, Joseph, Bergenstråhle, Ludvig, Bolt, Liam, Braun, Emelie, Bui, Linh T., Callori, Steven, Chaffin, Mark, Chichelnitskiy, Evgeny, Chiou, Joshua, Conlon, Thomas M., Cuoco, Michael S., Cuomo, Anna S. E., Deprez, Marie, Duclos, Grant, Fine, Denise, Fischer, David S., Ghazanfar, Shila, Gillich, Astrid, Giotti, Bruno, Gould, Joshua, Guo, Minzhe, Gutierrez, Austin J., Habermann, Arun C., Harvey, Tyler, He, Peng, Hou, Xiaomeng, Hu, Lijuan, Hu, Yan, Jaiswal, Alok, Ji, Lu, Jiang, Peiyong, Kapellos, Theodoros S., Kuo, Christin S., Larsson, Ludvig, Leney-Greene, Michael A., Lim, Kyungtae, Litviňuková, Monika, Ludwig, Leif S., Lukassen, Soeren, Luo, Wendy, Maatz, Henrike, Madissoon, Elo, Mamanova, Lira, Manakongtreecheep, Kasidet, Leroy, Sylvie, Mayr, Christoph H., Mbano, Ian M., McAdams, Alexi M., Nabhan, Ahmad N., Nyquist, Sarah K., Penland, Lolita, Poirion, Olivier B., Poli, Sergio, Qi, CanCan, Queen, Rachel, Reichart, Daniel, Rosas, Ivan, Schupp, Jonas C., Shea, Conor V., Shi, Xingyi, Sinha, Rahul, Sit, Rene V., Slowikowski, Kamil, Slyper, Michal, Smith, Neal P., Sountoulidis, Alex, Strunz, Maximilian, Sullivan, Travis B., Sun, Dawei, Talavera-López, Carlos, Tan, Peng, Tantivit, Jessica, Travaglini, Kyle J., Tucker, Nathan R., Vernon, Katherine A., Wadsworth, Marc H., Waldman, Julia, Wang, Xiuting, Xu, Ke, Yan, Wenjun, Zhao, William, Ziegler, Carly G. K., The NHLBI LungMap Consortium, Deutsch, Gail H., Dutra, Jennifer, Gaulton, Kyle J., Holden-Wiltse, Jeanne, Huyck, Heidie L., Mariani, Thomas J., Misra, Ravi S., Poole, Cory, Preissl, Sebastian, Pryhuber, Gloria S., Rogers, Lisa, Sun, Xin, Wang, Allen, Whitsett, Jeffrey A., Xu, Yan, The Human Cell Atlas Lung Biological Network, Alladina, Jehan, Banovich, Nicholas E., Barbry, Pascal, Beane, Jennifer E., Bhattacharyya, Roby P., Black, Katharine E., Brazma, Alvis, Campbell, Joshua D., Cho, Josalyn L., Collin, Joseph, Conrad, Christian, de Jong, Kitty, Desai, Tushar, Ding, Diane Z., Eickelberg, Oliver, Eils, Roland, Ellinor, Patrick T., Faiz, Alen, Falk, Christine S., Farzan, Michael, Gellman, Andrew, Getz, Gad, Glass, Ian A., Greka, Anna, Haniffa, Muzlifah, Hariri, Lida P., Hennon, Mark W., Horvath, Peter, Hübner, Norbert, Hung, Deborah T., Huyck, Heidie L., Janssen, William J., Juric, Dejan, Kaminski, Naftali, Koenigshoff, Melanie, Koppelman, Gerard H., Krasnow, Mark A., Kropski, Jonathan A., Kuhnemund, Malte, Lafyatis, Robert, Lako, Majlinda, Lander, Eric S., Lee, Haeock, Lenburg, Marc E., Marquette, Charles-Hugo, Metzger, Ross J., Linnarsson, Sten, Liu, Gang, Lo, Yuk Ming Dennis, Lundeberg, Joakim, Marioni, John C., Mazzilli, Sarah A., Medoff, Benjamin D., Meyer, Kerstin B., Miao, Zhichao, Misharin, Alexander V., Nawijn, Martijn C., Nikolić, Marko Z., Noseda, Michela, Ordovas-Montanes, Jose, Oudit, Gavin Y., Pe’er, Dana, Powell, Joseph E., Quake, Stephen R., Rajagopal, Jayaraj, Tata, Purushothama Rao, Rawlins, Emma L., Regev, Aviv, Reid, Mary E., Reyfman, Paul A., Rieger-Christ, Kimberly M., Rojas, Mauricio, Rozenblatt-Rosen, Orit, Saeb-Parsy, Kourosh, Samakovlis, Christos, Sanes, Joshua R., Schiller, Herbert B., Schultze, Joachim L., Schwarz, Roland F., Segre, Ayellet V., Seibold, Max A., Seidman, Christine E., Seidman, Jon G., Shalek, Alex K., Shepherd, Douglas P., Sinha, Rahul, Spence, Jason R., Spira, Avrum, Sun, Xin, Sundström, Erik, Teichmann, Sarah A., Theis, Fabian J., Tsankov, Alexander M., Vallier, Ludovic, van den Berge, Maarten, Van Zyl, Tave A., Villani, Alexandra-Chloé, Weins, Astrid, Xavier, Ramnik J., Yildirim, Ali Önder, Zaragosi, Laure-Emmanuelle, Zerti, Darin, Zhang, Hongbo, Zhang, Kun, Zhang, Xiaohui·2021·Nature Medicine
DOI 10.1038/s41591-020-01227-z
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Abstract

Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2 and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2+TMPRSS2+ cells in nasal, lung and gut tissues included genes that may mediate viral entry, key immune functions and epithelial–macrophage cross-talk, such as genes involved in the interleukin-6, interleukin-1, tumor necrosis factor and complement pathways. Cell-type-specific expression patterns may contribute to the pathogenesis of COVID-19, and our work highlights putative molecular pathways for therapeutic intervention. An integrated analysis of over 100 single-cell and single-nucleus transcriptomics studies illustrates severe acute respiratory syndrome coronavirus 2 viral entry gene coexpression patterns across different human tissues, and shows association of age, smoking status and sex with viral entry gene expression in respiratory cell populations.

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Metadata

Authors
Muus, C., Luecken, M. D., Eraslan, G., Sikkema, L., Waghray, A., Heimberg, G., Kobayashi, Y., Vaishnav, E. D., Subramanian, A., Smillie, C., Jagadeesh, K. A., Duong, E. T., Fiskin, E., Torlai Triglia, E., Ansari, M., Cai, P., Lin, B., Buchanan, J., Chen, S., Shu, J., Haber, A. L., Chung, H., Montoro, D. T., Adams, T., Aliee, H., Allon, S. J., Andrusivova, Z., Angelidis, I., Ashenberg, O., Bassler, K., Bécavin, C., Benhar, I., Bergenstråhle, J., Bergenstråhle, L., Bolt, L., Braun, E., Bui, L. T., Callori, S., Chaffin, M., Chichelnitskiy, E., Chiou, J., Conlon, T. M., Cuoco, M. S., Cuomo, A. S. E., Deprez, M., Duclos, G., Fine, D., Fischer, D. S., Ghazanfar, S., Gillich, A., Giotti, B., Gould, J., Guo, M., Gutierrez, A. J., Habermann, A. C., Harvey, T., He, P., Hou, X., Hu, L., Hu, Y., Jaiswal, A., Ji, L., Jiang, P., Kapellos, T. S., Kuo, C. S., Larsson, L., Leney-Greene, M. A., Lim, K., Litviňuková, M., Ludwig, L. S., Lukassen, S., Luo, W., Maatz, H., Madissoon, E., Mamanova, L., Manakongtreecheep, K., Leroy, S., Mayr, C. H., Mbano, I. M., McAdams, A. M., Nabhan, A. N., Nyquist, S. K., Penland, L., Poirion, O. B., Poli, S., Qi, C., Queen, R., Reichart, D., Rosas, I., Schupp, J. C., Shea, C. V., Shi, X., Sinha, R., Sit, R. V., Slowikowski, K., Slyper, M., Smith, N. P., Sountoulidis, A., Strunz, M., Sullivan, T. B., Sun, D., Talavera-López, C., Tan, P., Tantivit, J., Travaglini, K. J., Tucker, N. R., Vernon, K. A., Wadsworth, M. H., Waldman, J., Wang, X., Xu, K., Yan, W., Zhao, W., Ziegler, C. G. K., The NHLBI LungMap Consortium, Deutsch, G. H., Dutra, J., Gaulton, K. J., Holden-Wiltse, J., Huyck, H. L., Mariani, T. J., Misra, R. S., Poole, C., Preissl, S., Pryhuber, G. S., Rogers, L., Sun, X., Wang, A., Whitsett, J. A., Xu, Y., The Human Cell Atlas Lung Biological Network, Alladina, J., Banovich, N. E., Barbry, P., Beane, J. E., Bhattacharyya, R. P., Black, K. E., Brazma, A., Campbell, J. D., Cho, J. L., Collin, J., Conrad, C., de Jong, K., Desai, T., Ding, D. Z., Eickelberg, O., Eils, R., Ellinor, P. T., Faiz, A., Falk, C. S., Farzan, M., Gellman, A., Getz, G., Glass, I. A., Greka, A., Haniffa, M., Hariri, L. P., Hennon, M. W., Horvath, P., Hübner, N., Hung, D. T., Huyck, H. L., Janssen, W. J., Juric, D., Kaminski, N., Koenigshoff, M., Koppelman, G. H., Krasnow, M. A., Kropski, J. A., Kuhnemund, M., Lafyatis, R., Lako, M., Lander, E. S., Lee, H., Lenburg, M. E., Marquette, C.-H., Metzger, R. J., Linnarsson, S., Liu, G., Lo, Y. M. D., Lundeberg, J., Marioni, J. C., Mazzilli, S. A., Medoff, B. D., Meyer, K. B., Miao, Z., Misharin, A. V., Nawijn, M. C., Nikolić, M. Z., Noseda, M., Ordovas-Montanes, J., Oudit, G. Y., Pe’er, D., Powell, J. E., Quake, S. R., Rajagopal, J., Tata, P. R., Rawlins, E. L., Regev, A., Reid, M. E., Reyfman, P. A., Rieger-Christ, K. M., Rojas, M., Rozenblatt-Rosen, O., Saeb-Parsy, K., Samakovlis, C., Sanes, J. R., Schiller, H. B., Schultze, J. L., Schwarz, R. F., Segre, A. V., Seibold, M. A., Seidman, C. E., Seidman, J. G., Shalek, A. K., Shepherd, D. P., Sinha, R., Spence, J. R., Spira, A., Sun, X., Sundström, E., Teichmann, S. A., Theis, F. J., Tsankov, A. M., Vallier, L., van den Berge, M., Van Zyl, T. A., Villani, A.-C., Weins, A., Xavier, R. J., Yildirim, A. Ö., Zaragosi, L.-E., Zerti, D., Zhang, H., Zhang, K., & Zhang, X.
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
2021-03
Volume
27
Issue
3
Pages
546-559
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
DOI
10.1038/s41591-020-01227-z
OpenAlex
W3134181354
Cited by
348
References
25
FWCI
10.08
Type
journal article
Language
en
Open access
hybrid
Licence

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