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

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...

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Vydáno v:	Nature medicine Ročník 27; číslo 3; s. 546 - 559
Hlavní autoři:	Luecken, Malte D., Sikkema, Lisa, Waghray, Avinash, Heimberg, Graham, Kobayashi, Yoshihiko, Vaishnav, Eeshit Dhaval, Subramanian, Ayshwarya, Smillie, Christopher, Jagadeesh, Karthik A., Duong, Elizabeth Thu, Torlai Triglia, Elena, Ansari, Meshal, Cai, Peiwen, Lin, Brian, Chen, Sijia, Shu, Jian, Haber, Adam L., Chung, Hattie, Montoro, Daniel T., Adams, Taylor, Aliee, Hananeh, Andrusivova, Zaneta, Angelidis, Ilias, Ashenberg, Orr, Bassler, Kevin, Bécavin, Christophe, Benhar, Inbal, Bergenstråhle, Joseph, Bergenstråhle, Ludvig, Braun, Emelie, Bui, Linh T., Chaffin, Mark, Chichelnitskiy, Evgeny, Chiou, Joshua, Conlon, Thomas M., Cuoco, Michael S., Cuomo, Anna S. E., Deprez, Marie, Duclos, Grant, 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, Yan, Jaiswal, Alok, Ji, Lu, Jiang, Peiyong, Kapellos, Theodoros S., Kuo, Christin S., 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., 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, Slowikowski, Kamil, 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, Yan, Wenjun, Zhao, William, Ziegler, Carly G. K.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	New York Nature Publishing Group US 01.03.2021 Nature Publishing Group
Témata:	631/114 631/250 631/326/596/4130 631/337/2019 692/699/255/2514 ACE2 Adult Age Aged Aged, 80 and over Alveolar Epithelial Cells - metabolism Alveolar Epithelial Cells - virology Alveoli Analysis Angiotensin Angiotensin-converting enzyme 2 Angiotensin-Converting Enzyme 2 - genetics Angiotensin-Converting Enzyme 2 - metabolism Biomedical and Life Sciences Biomedicine Cancer Research Cathepsin L - genetics Cathepsin L - metabolism Coronaviridae Coronaviruses COVID-19 COVID-19 - epidemiology COVID-19 - genetics COVID-19 - pathology COVID-19 - virology Crosstalk Cytokines Datasets as Topic - statistics & numerical data Demographic aspects Demographics Demography Disease transmission Epidemics Epithelial cells Female Gene expression Gene Expression Profiling - statistics & numerical data Gene sequencing Genes Genetic aspects Host-Pathogen Interactions - genetics Human tissues Humans Infectious Diseases Interleukin 1 Interleukin 6 Lung - metabolism Lung - virology Lungs Macrophages Male Meta-analysis Metabolic Diseases Middle Aged Molecular Medicine Neurosciences Organ Specificity - genetics Organs Parenchyma Pathogenesis Peptidyl-dipeptidase A Quorum sensing Respiration Respiratory diseases Respiratory System - metabolism Respiratory System - virology Respiratory tract Ribonucleic acid RNA SARS-CoV-2 - physiology Sequence Analysis, RNA - methods Sequence Analysis, RNA - statistics & numerical data Serine Endopeptidases - genetics Serine Endopeptidases - metabolism Severe acute respiratory syndrome coronavirus 2 Sex Single-Cell Analysis - methods Single-Cell Analysis - statistics & numerical data Smoking Transcriptomics Tropism United States Viral diseases Virus Internalization United States
ISSN:	1078-8956, 1546-170X, 1546-170X
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Popis
Shrnutí:	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.
Bibliografie:	ObjectType-Article-2 SourceType-Scholarly Journals-1 content type line 14 ObjectType-Feature-3 ObjectType-Evidence Based Healthcare-1 ObjectType-Article-1 ObjectType-Feature-2 content type line 23 C.M., A.W., Y.K., E.T.D., B.L., D.T.M., T.S.A., S.J.A., Z.A., I.A., K.B., J.B., Lu.B., Li.B., E.B., L.T.B., S.C., E.C., T.M.C., M.S.C., S.G., A.G., X.H., L.H., Y.H., T.S.K., M.L., L.S.L., W.L., H.M., E.M., L.M., K.M., I.M.M., A.M.M., A.N.N., S.K.N., L.P., C.Q., D.R., R.V.S., M.S., N.P.S., M.S., D.S., J.T., K.J.T., M.H.W., J.W., W.Y., C.G.K.Z. performed experiments These authors contributed equally A.R., C.M., M.D.L., G.E., L.S., A.W., G.H., E.D.V., A.S., C.S.S., K.A.J., E.F., E.T.T., B.L., S.C., J.S., A.L.H., D.T.M. wrote the manuscript with input from all authors and guidance from A.R., J.R., F.J.T., M.C.N. principal investigators listed in The Human Cell Atlas Lung Biological Network authors provided resources. C.M., M.D.L., G.E., L.S., A.W., Y.K., G.H., E.D.V., A.S., C.S.S., K.A.J., E.T.D., E.F., E.T.T., M.A., P.C., B.L., J.B., S.C., J.S., A.L.H., H.C., D.T.M. analyzed and interpreted data with input from T.S.A., H.A., S.J.A., O.A., C.B., I.B., M.C., J.C., T.M.C., A.S.C., M.D., G.D., D.S.F., S.G., A.G., B.G., J.G., M.G., A.C.H., T.H., P.H., A.J., L.J., P.J., T.S.K., L.L., M.A.L., S.L., H.M., E.M., C.H.M., I.M.M., A.M.M., L.P., A.N.N., O.B.P., S.P., S.K.N., R.Q., D.R., C.V.S., X.S., R.S., K.S., T.B.S., C.T., P.T., K.J.T., N.R.T., M.H.W., X.W., W.Y., W.Z., C.G.Z. sample collection was performed by A.W., B.L., D.T.M., S.L., I.R., J.C.S., M.S., K.A.V. and HCA Lung Biological Network Author Contributions
ISSN:	1078-8956 1546-170X 1546-170X
DOI:	10.1038/s41591-020-01227-z