Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics.
Adult
Aged
Aged, 80 and over
Alveolar Epithelial Cells
/ metabolism
Angiotensin-Converting Enzyme 2
/ genetics
COVID-19
/ epidemiology
Cathepsin L
/ genetics
Datasets as Topic
/ statistics & numerical data
Demography
Female
Gene Expression Profiling
/ statistics & numerical data
Host-Pathogen Interactions
/ genetics
Humans
Lung
/ metabolism
Male
Middle Aged
Organ Specificity
/ genetics
Respiratory System
/ metabolism
SARS-CoV-2
/ physiology
Sequence Analysis, RNA
/ methods
Serine Endopeptidases
/ genetics
Single-Cell Analysis
/ methods
Virus Internalization
Journal
Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
16
04
2020
accepted:
23
12
2020
pubmed:
4
3
2021
medline:
27
3
2021
entrez:
3
3
2021
Statut:
ppublish
Résumé
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
Identifiants
pubmed: 33654293
doi: 10.1038/s41591-020-01227-z
pii: 10.1038/s41591-020-01227-z
pmc: PMC9469728
mid: NIHMS1757283
doi:
Substances chimiques
ACE2 protein, human
EC 3.4.17.23
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
Serine Endopeptidases
EC 3.4.21.-
TMPRSS2 protein, human
EC 3.4.21.-
CTSL protein, human
EC 3.4.22.15
Cathepsin L
EC 3.4.22.15
Types de publication
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
546-559Subventions
Organisme : NHLBI NIH HHS
ID : K08 HL130595
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL127349
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK043351
Pays : United States
Organisme : Medical Research Council
ID : MR/S035907/1
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : U01 HL148867
Pays : United States
Organisme : Medical Research Council
ID : MR/S035826/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P009581/1
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL130938
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL145567
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL145550
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL148861
Pays : United States
Organisme : NHLBI NIH HHS
ID : F32 HL149290
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL141380
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL119215
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL148856
Pays : United States
Organisme : NIDDK NIH HHS
ID : RC2 DK114784
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI116482
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL145372
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL122700
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG049665
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007753
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK117263
Pays : United States
Organisme : NHLBI NIH HHS
ID : K08 HL146943
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI135964
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL080494
Pays : United States
Organisme : NICHD NIH HHS
ID : R24 HD000836
Pays : United States
Organisme : NHLBI NIH HHS
ID : R35 HL140039
Pays : United States
Organisme : Medical Research Council
ID : MR/S005579/1
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL146519
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : U24 AI118672
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL133153
Pays : United States
Organisme : British Heart Foundation
ID : SP/19/1/34461
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL146557
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI142784
Pays : United States
Organisme : NHLBI NIH HHS
ID : R56 HL135124
Pays : United States
Investigateurs
Gail H Deutsch
(GH)
Jennifer Dutra
(J)
Kyle J Gaulton
(KJ)
Jeanne Holden-Wiltse
(J)
Heidie L Huyck
(HL)
Thomas J Mariani
(TJ)
Ravi S Misra
(RS)
Cory Poole
(C)
Sebastian Preissl
(S)
Gloria S Pryhuber
(GS)
Lisa Rogers
(L)
Xin Sun
(X)
Allen Wang
(A)
Jeffrey A Whitsett
(JA)
Yan Xu
(Y)
Jehan Alladina
(J)
Nicholas E Banovich
(NE)
Pascal Barbry
(P)
Jennifer E Beane
(JE)
Roby P Bhattacharyya
(RP)
Katharine E Black
(KE)
Alvis Brazma
(A)
Joshua D Campbell
(JD)
Josalyn L Cho
(JL)
Joseph Collin
(J)
Christian Conrad
(C)
Kitty de Jong
(K)
Tushar Desai
(T)
Diane Z Ding
(DZ)
Oliver Eickelberg
(O)
Roland Eils
(R)
Patrick T Ellinor
(PT)
Alen Faiz
(A)
Christine S Falk
(CS)
Michael Farzan
(M)
Andrew Gellman
(A)
Gad Getz
(G)
Ian A Glass
(IA)
Anna Greka
(A)
Muzlifah Haniffa
(M)
Lida P Hariri
(LP)
Mark W Hennon
(MW)
Peter Horvath
(P)
Norbert Hübner
(N)
Deborah T Hung
(DT)
Heidie L Huyck
(HL)
William J Janssen
(WJ)
Dejan Juric
(D)
Naftali Kaminski
(N)
Melanie Koenigshoff
(M)
Gerard H Koppelman
(GH)
Mark A Krasnow
(MA)
Jonathan A Kropski
(JA)
Malte Kuhnemund
(M)
Robert Lafyatis
(R)
Majlinda Lako
(M)
Eric S Lander
(ES)
Haeock Lee
(H)
Marc E Lenburg
(ME)
Charles-Hugo Marquette
(CH)
Ross J Metzger
(RJ)
Sten Linnarsson
(S)
Gang Liu
(G)
Yuk Ming Dennis Lo
(YMD)
Joakim Lundeberg
(J)
John C Marioni
(JC)
Sarah A Mazzilli
(SA)
Benjamin D Medoff
(BD)
Kerstin B Meyer
(KB)
Zhichao Miao
(Z)
Alexander V Misharin
(AV)
Martijn C Nawijn
(MC)
Marko Z Nikolić
(MZ)
Michela Noseda
(M)
Jose Ordovas-Montanes
(J)
Gavin Y Oudit
(GY)
Dana Pe'er
(D)
Joseph E Powell
(JE)
Stephen R Quake
(SR)
Jayaraj Rajagopal
(J)
Purushothama Rao Tata
(PR)
Emma L Rawlins
(EL)
Aviv Regev
(A)
Mary E Reid
(ME)
Paul A Reyfman
(PA)
Kimberly M Rieger-Christ
(KM)
Mauricio Rojas
(M)
Orit Rozenblatt-Rosen
(O)
Kourosh Saeb-Parsy
(K)
Christos Samakovlis
(C)
Joshua R Sanes
(JR)
Herbert B Schiller
(HB)
Joachim L Schultze
(JL)
Roland F Schwarz
(RF)
Ayellet V Segre
(AV)
Max A Seibold
(MA)
Christine E Seidman
(CE)
Jon G Seidman
(JG)
Alex K Shalek
(AK)
Douglas P Shepherd
(DP)
Rahul Sinha
(R)
Jason R Spence
(JR)
Avrum Spira
(A)
Xin Sun
(X)
Erik Sundström
(E)
Sarah A Teichmann
(SA)
Fabian J Theis
(FJ)
Alexander M Tsankov
(AM)
Ludovic Vallier
(L)
Maarten van den Berge
(M)
Tave A Van Zyl
(TA)
Alexandra-Chloé Villani
(AC)
Astrid Weins
(A)
Ramnik J Xavier
(RJ)
Ali Önder Yildirim
(AÖ)
Laure-Emmanuelle Zaragosi
(LE)
Darin Zerti
(D)
Hongbo Zhang
(H)
Kun Zhang
(K)
Xiaohui Zhang
(X)
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