Abstract
We investigated SARS-CoV-2 potential tropism by surveying expression of viral entry-associated genes in single-cell RNA-sequencing data from multiple tissues from healthy human donors. We co-detected these transcripts in specific respiratory, corneal and intestinal epithelial cells, potentially explaining the high efficiency of SARS-CoV-2 transmission. These genes are co-expressed in nasal epithelial cells with genes involved in innate immunity, highlighting the cells’ potential role in initial viral infection, spread and clearance. The study offers a useful resource for further lines of inquiry with valuable clinical samples from COVID-19 patients and we provide our data in a comprehensive, open and user-friendly fashion at www.covid19cellatlas.org.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 681-687 |
| Number of pages | 7 |
| Journal | Nature Medicine |
| Volume | 26 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 1 2020 |
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
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SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. / HCA Lung Biological Network.
In: Nature Medicine, Vol. 26, No. 5, 01.05.2020, p. 681-687.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes
AU - HCA Lung Biological Network
AU - Sungnak, Waradon
AU - Huang, Ni
AU - Bécavin, Christophe
AU - Berg, Marijn
AU - Queen, Rachel
AU - Litvinukova, Monika
AU - Talavera-López, Carlos
AU - Maatz, Henrike
AU - Reichart, Daniel
AU - Sampaziotis, Fotios
AU - Worlock, Kaylee B.
AU - Yoshida, Masahiro
AU - Barnes, Josephine L.
AU - Banovich, Nicholas E.
AU - Barbry, Pascal
AU - Brazma, Alvis
AU - Collin, Joseph
AU - Desai, Tushar J.
AU - Duong, Thu Elizabeth
AU - Eickelberg, Oliver
AU - Falk, Christine
AU - Farzan, Michael
AU - Glass, Ian
AU - Gupta, Ravindra K.
AU - Haniffa, Muzlifah
AU - Horvath, Peter
AU - Hubner, Norbert
AU - Hung, Deborah
AU - Kaminski, Naftali
AU - Krasnow, Mark
AU - Kropski, Jonathan A.
AU - Kuhnemund, Malte
AU - Lako, Majlinda
AU - Lee, Haeock
AU - Leroy, Sylvie
AU - Linnarson, Sten
AU - Lundeberg, Joakim
AU - Meyer, Kerstin B.
AU - Miao, Zhichao
AU - Misharin, Alexander V.
AU - Nawijn, Martijn C.
AU - Nikolic, Marko Z.
AU - Noseda, Michela
AU - Ordovas-Montanes, Jose
AU - Oudit, Gavin Y.
AU - Pe’er, Dana
AU - Powell, Joseph
AU - Quake, Steve
AU - Rajagopal, Jay
AU - Shepherd, Douglas
N1 - Funding Information: N.K. was a consultant to Biogen Idec, Boehringer Ingelheim, Third Rock, Pliant, Samumed, NuMedii, Indaloo, Theravance, LifeMax, Three Lake Partners and Optikira in the last 3 years and received nonfinancial support from MiRagen. J.L. is a scientific consultant for 10X Genomics. J.K. reports advisory board fees from Boehringer Ingelheim, nonfinancial study support from Genentech and grant funding from Boehringer Ingelheim. A.R. is a co-founder and equity holder of Celsius Therapeutics, an equity holder in Immunitas and an SAB member of Thermo Fisher Scientific, Syros Pharmaceuticals, Asimov and Neogene Therapeutics. O.R. is a co-inventor on patent applications filed by the Broad Institute to inventions relating to single-cell genomics applications, such as in PCT/US2018/060860 and US Provisional Application No. 62/745,259. A.K.S. reports compensation for consulting and/or SAB membership from Merck, Honeycomb Biotechnologies, Cellarity, Cogen Therapeutics, Orche Bio and Dahlia Biosciences. F.J.T. reports receiving consulting fees from Roche Diagnostics GmbH and ownership interest in Cellarity Inc. S.A.T. was a consultant at Genentech, Biogen and Roche in the last 3 years. L.V. is a founder of Definigen and Bilitech, two biotech companies using hPSCs and organoid for disease modeling and cell-based therapy. F.S. is a founder of Bilitech, a biotechnology company using organoids for cell-based therapy. Funding Information: We are grateful to C. Bargmann, J. Farrar and S. Aldridge for stimulating discussions. We thank J. Eliasova (scientific illustrator) for support with the design of figures, S. Sansum for support in document processing and M. Prete, V. Kiselev and the Wellcome Sanger Cellular Genetics IT Team, as well as P. Bevan, for support with setting up the website portal. The human embryonic and fetal material was provided by the Joint Medical Research Council (MRC)/Wellcome (MR/R006237/1) Human Developmental Biology Resource (www.hdbr.org). This publication is part of the HCA (www.humancellatlas. org/publications). This work was supported by the Wellcome Sanger Institute core funding (WT206194) and the Wellcome Strategic Scientific Support award ‘Pilot projects for the Human Cell Atlas’ (WT211276/Z/18/Z), a Seed Network grant from the Chan Zuckerberg Initiative to P.B., T.D., T.E.D., O.E., P.H., N.H., N.K., M.K., K.B.M., A.M., M.C.N., M.N., D.P., J.R., P.R.T., S.Q., A.R., O.R., M.A.S., J.S., J.G.S., C.E.S., H.B.S., D.S., A.M.T., J.W. and K.Z. and by the European Union’s H2020 Research and Innovation Program under grant agreement no. 874656 (discovAIR) to P.B., A.B., M.K., S.L., J.L., K.B.M., M.C.N., K.S.P., C.S., H.B.S., J.S., F.J.T. and M.vd.B. W.S. acknowledges funding from the Newton Fund, MRC, The Thailand Research Fund and Thailand’s National Science and Technology Development Agency. M.C.N acknowledges funding from GSK Ltd., Netherlands Lung Foundation project no. 5.1.14.020 and 4.1.18.226. T.D. acknowledges funding from HubMap consortium and Stanford Child Health Research Institute-Woods Family Faculty Scholarship. T.E.D. acknowledges funding from HubMap. P.H. acknowledges funding from LENDULET-BIOMAG grant (2018-342) and the European Regional Development Fund (GINOP-2.3.2-15-2016-00006, GINOP-2.3.2-15-2016-00026, GINOP-2.3.2-15-2016-00037). J.L.B. acknowledges funding from the MRC and the UK Regenerative Medicine Platform (MR/5005579/1). P.B. acknowledges funding from Fondation pour la Recherche Médicale (DEQ20180339158), Agence Nationale de la Recherche (UCAJEDI, ANR-15-IDEX-01; SAHARRA, ANR-19-CE14-0027; France Génomique, ANR-10-INBS-09-03) and Conseil Départemental des Alpes Maritimes (2016-294DGADSH-CV; 2019-390DGADSH-CV). N.E.B. and J.K. acknowledge funding from National Institutes of Health (NIH) grant R01HL145372 and DOD grant W81XWH1910416. I.G. acknowledges funding from NIH (5R24HD000836) and the Eunice Kennedy Shriver National Institute of Child Health and Human. N.H., J.G.S. and C.E.S. acknowledge funding by the Leducq foundation. N.H. is recipient of an ERC Advanced grant. J.K. acknowledges funding from NIH grant K08HL130595 and the Doris Duke Charitable Foundation. N.K. acknowledges funding from NIH grants R01HL127349, U01HL145567 and an unrestricted grant from Three Lakes Foundation. M.K. acknowledges HHMI and Wall Center for Pulmonary Vascular Disease. H.L. acknowledges funding from National Research Foundation of Korea. K.M. acknowledges funding from Wellcome Trust. A.M. acknowledges funding from NIH grants HL135124, AG049665 and AI135964. M.Z.N. acknowledges funding from Rutherford Fund Fellowship allocated by the MRC and the UK Regenerative Medicine Platform (MR/5005579/1 to M.Z.N.). M.Z.N. and M.Y. have been funded by the Rosetrees Trust (M899). M.N. acknowledges funding from a BHF/DZHK grant and British Heart Foundation (PG/16/47/32156). J.O.-M. acknowledges funding from Richard and Susan Smith Family Foundation. D.P. acknowledges funding from Alan and Sandra Gerry Metastasis and Tumor Ecosystems Center. J.P. acknowledges funding from National Health and MRC. P.R.T. acknowledges funding from R01HL146557 from NHLBI/NIH. E.L.R. acknowledges funding from MRC MR/P009581/1 and MR/ SO35907/1. A.R. and O. R. acknowledge HHMI, the Klarman Cell Observatory and the Manton Foundation. K.S.-P. acknowledges NIHR Cambridge Biomedical Research Centre. C.S. acknowledges the Swedish Research Council, Swedish Cancer Society and CPI. H.B.S. acknowledges the German Center for Lung Research and the Helmholtz Association. J.S. acknowledges Boehringer Ingelheim, by the German Research Foundation (DFG; EXC2151/1, ImmunoSensation2, the immune sensory system, project no. 390873048), project nos. 329123747, 347286815) and by the HGF grant sparse2big. A.K.S. acknowledges the Beckman Young Investigator Program, a Sloan Fellowship in Chemistry, the NIH (5U24AI118672) and the Bill and Melinda Gates Foundation. F.J.T. acknowledges the German Center for Lung Research. M.vd.B. acknowledges the Ministry of Economic Affairs and Climate Policy by means of the PPP. K.B.W. is funded by the University College London, Birkbeck MRC Doctoral Training Programme. J.W. and Y.Y. acknowledge NIH, U01 HL148856 LungMap phase II. R.X. acknowledges the NIH (DK043351). H.Z. is supported by the National Key R&D Program (no. 2019YFA0801703) and National Natural Science Foundation of China (no. 31871370). M.A.S. acknowledges funding from NIH grants R01 HL135156, R01 MD010443, R01 HL128439, P01 HL132821, P01 HL107202, R01 HL117004, and DOD Grant W81WH-16-2-0018 and NJH Regenerative Medicine and Genome Editing Program (REGEN). Publisher Copyright: © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - We investigated SARS-CoV-2 potential tropism by surveying expression of viral entry-associated genes in single-cell RNA-sequencing data from multiple tissues from healthy human donors. We co-detected these transcripts in specific respiratory, corneal and intestinal epithelial cells, potentially explaining the high efficiency of SARS-CoV-2 transmission. These genes are co-expressed in nasal epithelial cells with genes involved in innate immunity, highlighting the cells’ potential role in initial viral infection, spread and clearance. The study offers a useful resource for further lines of inquiry with valuable clinical samples from COVID-19 patients and we provide our data in a comprehensive, open and user-friendly fashion at www.covid19cellatlas.org.
AB - We investigated SARS-CoV-2 potential tropism by surveying expression of viral entry-associated genes in single-cell RNA-sequencing data from multiple tissues from healthy human donors. We co-detected these transcripts in specific respiratory, corneal and intestinal epithelial cells, potentially explaining the high efficiency of SARS-CoV-2 transmission. These genes are co-expressed in nasal epithelial cells with genes involved in innate immunity, highlighting the cells’ potential role in initial viral infection, spread and clearance. The study offers a useful resource for further lines of inquiry with valuable clinical samples from COVID-19 patients and we provide our data in a comprehensive, open and user-friendly fashion at www.covid19cellatlas.org.
UR - http://www.scopus.com/inward/record.url?scp=85083969210&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85083969210&partnerID=8YFLogxK
U2 - 10.1038/s41591-020-0868-6
DO - 10.1038/s41591-020-0868-6
M3 - Article
C2 - 32327758
AN - SCOPUS:85083969210
VL - 26
SP - 681
EP - 687
JO - Nature Medicine
JF - Nature Medicine
SN - 1078-8956
IS - 5
ER -