Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics
Christoph Muus(Broad Institute), Malte D. Luecken(Helmholtz Zentrum München), Gökcen Eraslan(Broad Institute), Lisa Sikkema(Helmholtz Zentrum München), Avinash Waghray(Massachusetts General Hospital), Graham Heimberg(Broad Institute), Yoshihiko Kobayashi(Duke University), Eeshit Dhaval Vaishnav(Broad Institute), Ayshwarya Subramanian(Broad Institute), Christopher S. Smillie(Broad Institute), Karthik A. Jagadeesh(Broad Institute), Thu Elizabeth Duong(University of California San Diego), Evgenij Fiškin(Broad Institute), Elena Torlai Triglia(Broad Institute), Meshal Ansari(Helmholtz Zentrum München), Peiwen Cai(Icahn School of Medicine at Mount Sinai), Brian Lin(Massachusetts General Hospital), Justin Buchanan(University of California San Diego), Sijia Chen(Brigham and Women's Hospital), Jian Shu(Broad Institute), Adam L. Haber(Broad Institute), Hattie Chung(Broad Institute), Daniel T. Montoro(Broad Institute), Taylor Adams(Yale University), Hananeh Aliee(Helmholtz Zentrum München), Samuel J. Allon(Broad Institute), Žaneta Andrusivová(Science for Life Laboratory), Ilias Angelidis(Helmholtz Zentrum München), Orr Ashenberg(Broad Institute), Kevin Baßler(University of Bonn), Christophe Bécavin(Centre National de la Recherche Scientifique), Inbal Benhar(Broad Institute), Joseph Bergenstråhle(Science for Life Laboratory), Ludvig Bergenstråhle(Science for Life Laboratory), Liam Bolt(Wellcome Sanger Institute), Emelie Braun(Karolinska Institutet), Linh T. Bui(Translational Genomics Research Institute), Steven Callori(Boston University), Mark Chaffin(Broad Institute), Evgeny Chichelnitskiy(Medizinische Hochschule Hannover), Joshua Chiou(University of California San Diego), Thomas M. Conlon(Helmholtz Zentrum München), Michael S. Cuoco(Broad Institute), Anna Cuomo(European Bioinformatics Institute), Marie Deprez(Centre National de la Recherche Scientifique), Grant Duclos, Denise Fine(Boston University), David S. Fischer(Helmholtz Zentrum München), Shila Ghazanfar(University of Cambridge), Astrid Gillich(Center for Vascular Biology Research), Bruno Giotti(Icahn School of Medicine at Mount Sinai), Joshua Gould(Broad Institute), Minzhe Guo(Cincinnati Children's Hospital Medical Center), Austin J. Gutierrez(Translational Genomics Research Institute), Arun C. Habermann(Vanderbilt University Medical Center), Tyler Harvey(Broad Institute), Peng He(Wellcome Sanger Institute), Xiaomeng Hou(University of California San Diego), Lijuan Hu(Karolinska Institutet), Yan Hu(University of Colorado Anschutz Medical Campus), Alok Jaiswal(Broad Institute), Lu Ji(Chinese University of Hong Kong), Peiyong Jiang(Chinese University of Hong Kong), Theodoros Kapellos(University of Bonn), Christin S. Kuo(Stanford University), Ludvig Larsson(Science for Life Laboratory), Michael Leney-Greene(Broad Institute), Kyungtae Lim(University of Cambridge), Monika Litviňuková(Max Delbrück Center), Leif S. Ludwig(Broad Institute), Soeren Lukassen(Humboldt-Universität zu Berlin), Wendy Luo(Broad Institute), Henrike Maatz(Max Delbrück Center), Elo Madissoon(European Bioinformatics Institute), Lira Mamanova(Wellcome Sanger Institute), Kasidet Manakongtreecheep(Broad Institute), Sylvie Leroy(Centre National de la Recherche Scientifique), Christoph H. Mayr(Helmholtz Zentrum München), Ian Mbano(Africa Health Research Institute), Alexi McAdams(Massachusetts Eye and Ear Infirmary), Ahmad N. Nabhan(Center for Vascular Biology Research), Sarah K. Nyquist(Broad Institute), Lolita Penland(Center for Vascular Biology Research), Olivier Poirion(University of California San Diego), Sergio Poli(Yale University), Cancan Qi(University Medical Center Groningen), Rachel Queen(Centre for Life), Daniel Reichart(Harvard University), Iván O. Rosas(Yale University), Jonas C. Schupp(Yale University), Conor Shea(Boston University), Xingyi Shi(Boston University), Rahul Sinha(Boston University), Rene Sit(Center for Vascular Biology Research), Kamil Slowikowski(Broad Institute), Michal Slyper(Broad Institute), Neal P. Smith(Massachusetts General Hospital), Alex Sountoulidis(Stockholm University), Maximilian Strunz(Helmholtz Zentrum München), Travis Sullivan(Lahey Medical Center), Dawei Sun(University of Cambridge), Carlos Talavera‐López(Wellcome Sanger Institute), Peng Tan(Broad Institute), Jessica Tantivit(Broad Institute), Kyle J. Travaglini(Center for Vascular Biology Research), Nathan R. Tucker(Broad Institute), Katherine A. Vernon(Broad Institute), Marc H. Wadsworth(Broad Institute), Julia Waldman(Broad Institute), Xiuting Wang(Icahn School of Medicine at Mount Sinai), Ke Xu(Boston University), Wenjun Yan(Harvard University), William Zhao(Icahn School of Medicine at Mount Sinai), Carly G.K. Ziegler(Broad Institute), Gail Deutsch(Seattle Children's Hospital), Jennifer Dutra(University of Rochester Medical Center), Kyle J. Gaulton(University of California San Diego), Jeanne Holden‐Wiltse(University of Rochester Medical Center), Heidie Huyck(University of Rochester Medical Center), Thomas J. Mariani(University of Rochester Medical Center), Ravi Misra(University of Rochester Medical Center), Cory Poole(University of Rochester Medical Center), Sebastian Preißl(University of California San Diego), Gloria Pryhuber(University of Rochester Medical Center), Lisa M. Rogers(University of Rochester Medical Center), Xin Sun(University of California San Diego), Allen Wang(University of California San Diego), Jeffrey A. Whitsett(Cincinnati Children's Hospital Medical Center), Yan Xu(Cincinnati Children's Hospital Medical Center), The Human Cell Atlas Lung Biological Network(Massachusetts General Hospital), Jehan Alladina(Translational Genomics Research Institute), Nicholas E. Banovich(Centre National de la Recherche Scientifique), Pascal Barbry(Boston University), Jennifer Beane(Broad Institute), Roby P. Bhattacharyya(Massachusetts General Hospital), Katharine E. Black(European Bioinformatics Institute), Alvis Brāzma(Boston University), Joshua D. Campbell(Harvard University), Josalyn L. Cho(Centre for Life), Joseph Collin(Berlin Institute of Health at Charité - Universitätsmedizin Berlin), Christian Conrad(Roswell Park Comprehensive Cancer Center), Kitty de Jong(Stanford University), Tushar Desai(Boston University), Diane Z. Ding(University of Colorado Anschutz Medical Campus), Oliver Eickelberg(Berlin Institute of Health at Charité - Universitätsmedizin Berlin), Roland Eils(Broad Institute), Patrick T. Ellinor(University of Technology Sydney), Alen Faiz(Medizinische Hochschule Hannover), Christine S. Falk(Scripps Research Institute), Michael Farzan(Columbia University), Andrew J. Gellman(Broad Institute), Gad Getz(University of Washington), Ian A. Glass(Broad Institute), Anna Greka(Wellcome Sanger Institute), Muzlifah Haniffa(Harvard University), Lida P. Hariri(Roswell Park Comprehensive Cancer Center), Mark Hennon(HUN-REN Szegedi Biológiai Kutatóközpont), Péter Horváth(Max Delbrück Center), Norbert Hübner(Harvard University), Deborah T. Hung(University of Rochester Medical Center), Heidie L. Huyck(National Jewish Health), William J. Janssen(Harvard University), Dejan Juric(Yale University), Naftali Kaminski(University of Colorado Anschutz Medical Campus), M. Koenigshoff(University Medical Center Groningen), Gerard H. Koppelman(Center for Vascular Biology Research), Mark A. Krasnow(Vanderbilt University Medical Center), Jonathan A. Kropski, Malte Kühnemund(University of Pittsburgh Medical Center), Robert Lafyatis(Centre for Life), Majlinda Lako(Broad Institute), Eric S. Lander(Catholic University of Korea), Haeock Lee(Boston University), Marc E. Lenburg(Centre National de la Recherche Scientifique), Charles‐Hugo Marquette(Stanford University), Ross J. Metzger(Karolinska Institutet), Sten Linnarsson(Boston University), Gang Liu(Chinese University of Hong Kong), Yuk Ming Dennis Lo(Science for Life Laboratory), Joakim Lundeberg(European Bioinformatics Institute), John C. Marioni(Boston University), Sarah A. Mazzilli(Massachusetts General Hospital), Benjamin D. Medoff(Wellcome Sanger Institute), Kerstin B. Meyer(Wellcome Sanger Institute), Zhichao Miao(Northwestern University), Alexander V. Misharin(University Medical Center Groningen), Martijn C. Nawijn(University College London), Marko Nikolić(Imperial College London), Michela Noseda(Boston Children's Hospital), José Ordovás-Montañés(University of Alberta), Gavin Y. Oudit(Memorial Sloan Kettering Cancer Center), Dana Pe’er(Garvan Institute of Medical Research), Joseph E. Powell(Stanford University), Stephen R. Quake(Harvard Stem Cell Institute), Jayaraj Rajagopal(Duke University), Purushothama Rao Tata(University of Cambridge), Emma L. Rawlins(Howard Hughes Medical Institute), Aviv Regev(Roswell Park Comprehensive Cancer Center), Mary E. Reid(Northwestern University), Paul A. Reyfman(Lahey Medical Center), Kimberly Rieger‐Christ(University of Pittsburgh), Mauricio Rojas(Broad Institute), Orit Rozenblatt–Rosen(University of Cambridge), Kourosh Saeb‐Parsy(Stockholm University), Christos Samakovlis(Harvard University), Joshua R. Sanes(Helmholtz Zentrum München), Herbert B. Schiller(University of Bonn), Joachim L. Schultze(Max Delbrück Center), Roland F. Schwarz(Harvard University), Ayellet V. Segrè(National Jewish Health), Max A. Seibold(Harvard University), Christine E. Seidman(Harvard University), J.G. Seidman(Ragon Institute of MGH, MIT and Harvard), Alex K. Shalek(Arizona State University), Douglas P. Shepherd(California Institute for Regenerative Medicine), Rahul Sinha(California Institute for Regenerative Medicine), Jason R. Spence(Boston University), Avrum Spira(University of California San Diego), Xin Sun(Karolinska Institutet), Erik Sundström(Wellcome Sanger Institute), Sarah A. Teichmann(Helmholtz Zentrum München), Fabian J. Theis(Icahn School of Medicine at Mount Sinai), Alexander M. Tsankov(Wellcome/MRC Cambridge Stem Cell Institute), Ludovic Vallier(University Medical Center Groningen), Maarten van den Berge(Massachusetts Eye and Ear Infirmary), Tave A. Van Zyl(Massachusetts General Hospital), Alexandra–Chloé Villani(Brigham and Women's Hospital), Astrid Weins(Broad Institute), Ramnik J. Xavier(Koç University), Ali Önder Yildirim(Centre National de la Recherche Scientifique), Laure‐Emmanuelle Zaragosi(Centre for Life), Darin Zerti(Sun Yat-sen University), Hongbo Zhang(University of California San Diego), Kun Zhang(Boston University), Xiaohui Zhang
Cited by 372Open Access
Abstract
-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.
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