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

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Item Type:	Article
Title:	Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics
Creators Name:	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., Triglia, E.T., 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.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. and Ziegler, C.G.K.
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.
Keywords:	Alveolar Epithelial Cells, Angiotensin-Converting Enzyme 2, COVID-19, Cathepsin L, Datasets as Topic, Demography, Gene Expression Profiling, Host-Pathogen Interactions, Lung, Organ Specificity, RNA Sequence Analysis, Respiratory System, SARS-CoV-2, Serine Endopeptidases, Single-Cell Analysis, Virus Internalization
Source:	Nature Medicine
ISSN:	1078-8956
Publisher:	Nature Publishing Group
Volume:	27
Number:	3
Page Range:	546-559
Date:	2 March 2021
Additional Information:	Norbert Hübner and Roland F. Schwarz are members of the Human Cell Atlas Lung Biological Network. Copyright © The Author(s), under exclusive licence to Springer Nature America, Inc. 2021
Official Publication:	https://doi.org/10.1038/s41591-020-01227-z
External Fulltext:	View full text on PubMed Central
PubMed:	View item in PubMed

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