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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... Full description

Journal Title: Nature medicine 2021, Vol.27 (3), p.546-559
Main Author: Muus, Christoph
Other Authors: Luecken, Malte D , Eraslan, Gökcen , Sikkema, Lisa , Waghray, Avinash , Heimberg, Graham , Kobayashi, Yoshihiko , Vaishnav, Eeshit Dhaval , Subramanian, Ayshwarya , Smillie, Christopher , Jagadeesh, Karthik A , Duong, Elizabeth Thu , Fiskin, Evgenij , Triglia, Elena Torlai , Ansari, Meshal , Cai, Peiwen , Lin, Brian , Buchanan, Justin , Chen, Sijia , Shu, Jian , Haber, Adam L , Chung, Hattie , Montoro, Daniel T , Adams, Taylor , Aliee, Hananeh , Allon, Samuel J , Anusivova, Zaneta , Angelidis, Ilias , Ashenberg, Orr , Bassler, Kevin , Bécavin, Christophe , Benhar, Inbal , Bergenstråhle, Joseph , Bergenstråhle, Ludvig , Bolt, Liam , Braun, Emelie , Bui, Linh T , Callori, Steven , Chaffin, Mark , Chichelnitskiy, Evgeny , Chiou, Joshua , Conlon, Thomas M , Cuoco, Michael S , Cuomo, Anna S E , Deprez, Marie , Duclos, Grant , Fine, Denise , Fischer, David S , Hu, Yan , Qi, CanCan
Format: Electronic Article Electronic Article
Language: English
Subjects:
Age
RNA
Sex
Publisher: United States: Nature Publishing Group
ID: ISSN: 1078-8956
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title: Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics
format: Article
creator:
  • Muus, Christoph
  • Luecken, Malte D
  • Eraslan, Gökcen
  • Sikkema, Lisa
  • Waghray, Avinash
  • Heimberg, Graham
  • Kobayashi, Yoshihiko
  • Vaishnav, Eeshit Dhaval
  • Subramanian, Ayshwarya
  • Smillie, Christopher
  • Jagadeesh, Karthik A
  • Duong, Elizabeth Thu
  • Fiskin, Evgenij
  • Triglia, Elena Torlai
  • Ansari, Meshal
  • Cai, Peiwen
  • Lin, Brian
  • Buchanan, Justin
  • Chen, Sijia
  • Shu, Jian
  • Haber, Adam L
  • Chung, Hattie
  • Montoro, Daniel T
  • Adams, Taylor
  • Aliee, Hananeh
  • Allon, Samuel J
  • Anusivova, Zaneta
  • Angelidis, Ilias
  • Ashenberg, Orr
  • Bassler, Kevin
  • Bécavin, Christophe
  • Benhar, Inbal
  • Bergenstråhle, Joseph
  • Bergenstråhle, Ludvig
  • Bolt, Liam
  • Braun, Emelie
  • Bui, Linh T
  • Callori, Steven
  • Chaffin, Mark
  • Chichelnitskiy, Evgeny
  • Chiou, Joshua
  • Conlon, Thomas M
  • Cuoco, Michael S
  • Cuomo, Anna S E
  • Deprez, Marie
  • Duclos, Grant
  • Fine, Denise
  • Fischer, David S
  • Hu, Yan
  • Qi, CanCan
subjects:
  • ACE2
  • Adult
  • Age
  • Aged
  • Aged, 80 and over
  • Alveolar Epithelial Cells - metabolism
  • Alveolar Epithelial Cells - virology
  • Alveoli
  • Angiotensin
  • Angiotensin-converting enzyme 2
  • Angiotensin-Converting Enzyme 2 - genetics
  • Angiotensin-Converting Enzyme 2 - metabolism
  • Basic Medicine
  • Cathepsin L - genetics
  • Cathepsin L - metabolism
  • Cell and Molecular Biology
  • Cell- och molekylärbiologi
  • Clinical Medicine
  • 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
  • Immunologi inom det medicinska området
  • Immunology in the medical area
  • Infectious Medicine
  • Infektionsmedicin
  • Interleukin
  • Interleukin 1
  • Interleukin 6
  • Klinisk medicin
  • Lung - metabolism
  • Lung - virology
  • Lungs
  • Macrophages
  • Male
  • Medical and Health Sciences
  • Medicin och hälsovetenskap
  • Medicinska och farmaceutiska grundvetenskaper
  • Middle Aged
  • Organ Specificity - genetics
  • Organs
  • Parenchyma
  • Pathogenesis
  • Pathways
  • 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
  • Severe acute respiratory syndrome coronavirus 2
  • Sex
  • Single-Cell Analysis - methods
  • Single-Cell Analysis - statistics & numerical data
  • Smoking
  • Tissues
  • Transcriptomics
  • Tropism
  • United States
  • Viral diseases
  • Virus Internalization
ispartof: Nature medicine, 2021, Vol.27 (3), p.546-559
description: 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.
language: eng
source:
identifier: ISSN: 1078-8956
fulltext: no_fulltext
issn:
  • 1078-8956
  • 1546-170X
  • 1546-170X
url: Link


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titleSingle-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics
creatorMuus, Christoph ; Luecken, Malte D ; Eraslan, Gökcen ; Sikkema, Lisa ; Waghray, Avinash ; Heimberg, Graham ; Kobayashi, Yoshihiko ; Vaishnav, Eeshit Dhaval ; Subramanian, Ayshwarya ; Smillie, Christopher ; Jagadeesh, Karthik A ; Duong, Elizabeth Thu ; Fiskin, Evgenij ; Triglia, Elena Torlai ; Ansari, Meshal ; Cai, Peiwen ; Lin, Brian ; Buchanan, Justin ; Chen, Sijia ; Shu, Jian ; Haber, Adam L ; Chung, Hattie ; Montoro, Daniel T ; Adams, Taylor ; Aliee, Hananeh ; Allon, Samuel J ; Anusivova, Zaneta ; Angelidis, Ilias ; Ashenberg, Orr ; Bassler, Kevin ; Bécavin, Christophe ; Benhar, Inbal ; Bergenstråhle, Joseph ; Bergenstråhle, Ludvig ; Bolt, Liam ; Braun, Emelie ; Bui, Linh T ; Callori, Steven ; Chaffin, Mark ; Chichelnitskiy, Evgeny ; Chiou, Joshua ; Conlon, Thomas M ; Cuoco, Michael S ; Cuomo, Anna S E ; Deprez, Marie ; Duclos, Grant ; Fine, Denise ; Fischer, David S ; Hu, Yan ; Qi, CanCan
creatorcontribMuus, Christoph ; Luecken, Malte D ; Eraslan, Gökcen ; Sikkema, Lisa ; Waghray, Avinash ; Heimberg, Graham ; Kobayashi, Yoshihiko ; Vaishnav, Eeshit Dhaval ; Subramanian, Ayshwarya ; Smillie, Christopher ; Jagadeesh, Karthik A ; Duong, Elizabeth Thu ; Fiskin, Evgenij ; Triglia, Elena Torlai ; Ansari, Meshal ; Cai, Peiwen ; Lin, Brian ; Buchanan, Justin ; Chen, Sijia ; Shu, Jian ; Haber, Adam L ; Chung, Hattie ; Montoro, Daniel T ; Adams, Taylor ; Aliee, Hananeh ; Allon, Samuel J ; Anusivova, Zaneta ; Angelidis, Ilias ; Ashenberg, Orr ; Bassler, Kevin ; Bécavin, Christophe ; Benhar, Inbal ; Bergenstråhle, Joseph ; Bergenstråhle, Ludvig ; Bolt, Liam ; Braun, Emelie ; Bui, Linh T ; Callori, Steven ; Chaffin, Mark ; Chichelnitskiy, Evgeny ; Chiou, Joshua ; Conlon, Thomas M ; Cuoco, Michael S ; Cuomo, Anna S E ; Deprez, Marie ; Duclos, Grant ; Fine, Denise ; Fischer, David S ; Hu, Yan ; Qi, CanCan ; NHLBI LungMap Consortium ; Human Cell Atlas Lung Biological Network ; The Human Cell Atlas Lung Biological Network ; The NHLBI LungMap Consortium
descriptionAngiotensin-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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1ISSN: 1546-170X
2EISSN: 1546-170X
3DOI: 10.1038/s41591-020-01227-z
4PMID: 33654293
languageeng
publisherUnited States: Nature Publishing Group
subjectACE2 ; Adult ; Age ; Aged ; Aged, 80 and over ; Alveolar Epithelial Cells - metabolism ; Alveolar Epithelial Cells - virology ; Alveoli ; Angiotensin ; Angiotensin-converting enzyme 2 ; Angiotensin-Converting Enzyme 2 - genetics ; Angiotensin-Converting Enzyme 2 - metabolism ; Basic Medicine ; Cathepsin L - genetics ; Cathepsin L - metabolism ; Cell and Molecular Biology ; Cell- och molekylärbiologi ; Clinical Medicine ; 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 ; Immunologi inom det medicinska området ; Immunology in the medical area ; Infectious Medicine ; Infektionsmedicin ; Interleukin ; Interleukin 1 ; Interleukin 6 ; Klinisk medicin ; Lung - metabolism ; Lung - virology ; Lungs ; Macrophages ; Male ; Medical and Health Sciences ; Medicin och hälsovetenskap ; Medicinska och farmaceutiska grundvetenskaper ; Middle Aged ; Organ Specificity - genetics ; Organs ; Parenchyma ; Pathogenesis ; Pathways ; 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 ; Severe acute respiratory syndrome coronavirus 2 ; Sex ; Single-Cell Analysis - methods ; Single-Cell Analysis - statistics & numerical data ; Smoking ; Tissues ; Transcriptomics ; Tropism ; United States ; Viral diseases ; Virus Internalization
ispartofNature medicine, 2021, Vol.27 (3), p.546-559
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0Muus, Christoph
1Luecken, Malte D
2Eraslan, Gökcen
3Sikkema, Lisa
4Waghray, Avinash
5Heimberg, Graham
6Kobayashi, Yoshihiko
7Vaishnav, Eeshit Dhaval
8Subramanian, Ayshwarya
9Smillie, Christopher
10Jagadeesh, Karthik A
11Duong, Elizabeth Thu
12Fiskin, Evgenij
13Triglia, Elena Torlai
14Ansari, Meshal
15Cai, Peiwen
16Lin, Brian
17Buchanan, Justin
18Chen, Sijia
19Shu, Jian
20Haber, Adam L
21Chung, Hattie
22Montoro, Daniel T
23Adams, Taylor
24Aliee, Hananeh
25Allon, Samuel J
26Anusivova, Zaneta
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28Ashenberg, Orr
29Bassler, Kevin
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33Bergenstråhle, Ludvig
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36Bui, Linh T
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48Hu, Yan
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title
0Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics
1Nature medicine
addtitleNat Med
descriptionAngiotensin-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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1Adult
2Age
3Aged
4Aged, 80 and over
5Alveolar Epithelial Cells - metabolism
6Alveolar Epithelial Cells - virology
7Alveoli
8Angiotensin
9Angiotensin-converting enzyme 2
10Angiotensin-Converting Enzyme 2 - genetics
11Angiotensin-Converting Enzyme 2 - metabolism
12Basic Medicine
13Cathepsin L - genetics
14Cathepsin L - metabolism
15Cell and Molecular Biology
16Cell- och molekylärbiologi
17Clinical Medicine
18Coronaviridae
19Coronaviruses
20COVID-19
21COVID-19 - epidemiology
22COVID-19 - genetics
23COVID-19 - pathology
24COVID-19 - virology
25Crosstalk
26Cytokines
27Datasets as Topic - statistics & numerical data
28Demographic aspects
29Demographics
30Demography
31Disease transmission
32Epidemics
33Epithelial cells
34Female
35Gene expression
36Gene Expression Profiling - statistics & numerical data
37Gene sequencing
38Genes
39Genetic aspects
40Host-Pathogen Interactions - genetics
41Human tissues
42Humans
43Immunologi inom det medicinska området
44Immunology in the medical area
45Infectious Medicine
46Infektionsmedicin
47Interleukin
48Interleukin 1
49Interleukin 6
50Klinisk medicin
51Lung - metabolism
52Lung - virology
53Lungs
54Macrophages
55Male
56Medical and Health Sciences
57Medicin och hälsovetenskap
58Medicinska och farmaceutiska grundvetenskaper
59Middle Aged
60Organ Specificity - genetics
61Organs
62Parenchyma
63Pathogenesis
64Pathways
65Peptidyl-dipeptidase A
66Quorum sensing
67Respiration
68Respiratory diseases
69Respiratory System - metabolism
70Respiratory System - virology
71Respiratory tract
72Ribonucleic acid
73RNA
74SARS-CoV-2 - physiology
75Sequence Analysis, RNA - methods
76Sequence Analysis, RNA - statistics & numerical data
77Serine Endopeptidases - genetics
78Serine Endopeptidases - metabolism
79Severe acute respiratory syndrome
80Severe acute respiratory syndrome coronavirus 2
81Sex
82Single-Cell Analysis - methods
83Single-Cell Analysis - statistics & numerical data
84Smoking
85Tissues
86Transcriptomics
87Tropism
88United States
89Viral diseases
90Virus Internalization
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20Haber, Adam L
21Chung, Hattie
22Montoro, Daniel T
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25Allon, Samuel J
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43Cuomo, Anna S E
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9https://orcid.org/0000-0003-3293-3158
sort
creationdate202103
titleSingle-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics
authorMuus, Christoph ; Luecken, Malte D ; Eraslan, Gökcen ; Sikkema, Lisa ; Waghray, Avinash ; Heimberg, Graham ; Kobayashi, Yoshihiko ; Vaishnav, Eeshit Dhaval ; Subramanian, Ayshwarya ; Smillie, Christopher ; Jagadeesh, Karthik A ; Duong, Elizabeth Thu ; Fiskin, Evgenij ; Triglia, Elena Torlai ; Ansari, Meshal ; Cai, Peiwen ; Lin, Brian ; Buchanan, Justin ; Chen, Sijia ; Shu, Jian ; Haber, Adam L ; Chung, Hattie ; Montoro, Daniel T ; Adams, Taylor ; Aliee, Hananeh ; Allon, Samuel J ; Anusivova, Zaneta ; Angelidis, Ilias ; Ashenberg, Orr ; Bassler, Kevin ; Bécavin, Christophe ; Benhar, Inbal ; Bergenstråhle, Joseph ; Bergenstråhle, Ludvig ; Bolt, Liam ; Braun, Emelie ; Bui, Linh T ; Callori, Steven ; Chaffin, Mark ; Chichelnitskiy, Evgeny ; Chiou, Joshua ; Conlon, Thomas M ; Cuoco, Michael S ; Cuomo, Anna S E ; Deprez, Marie ; Duclos, Grant ; Fine, Denise ; Fischer, David S ; Hu, Yan ; Qi, CanCan
facets
frbrtype5
frbrgroupidcdi_FETCH-LOGICAL-c696t-ba3c9611c3a28724ecfe225c7da779ab4b34e56fc32bc809c1405631a2a7a82f0
rsrctypearticles
prefilterarticles
languageeng
creationdate2021
topic
0ACE2
1Adult
2Age
3Aged
4Aged, 80 and over
5Alveolar Epithelial Cells - metabolism
6Alveolar Epithelial Cells - virology
7Alveoli
8Angiotensin
9Angiotensin-converting enzyme 2
10Angiotensin-Converting Enzyme 2 - genetics
11Angiotensin-Converting Enzyme 2 - metabolism
12Basic Medicine
13Cathepsin L - genetics
14Cathepsin L - metabolism
15Cell and Molecular Biology
16Cell- och molekylärbiologi
17Clinical Medicine
18Coronaviridae
19Coronaviruses
20COVID-19
21COVID-19 - epidemiology
22COVID-19 - genetics
23COVID-19 - pathology
24COVID-19 - virology
25Crosstalk
26Cytokines
27Datasets as Topic - statistics & numerical data
28Demographic aspects
29Demographics
30Demography
31Disease transmission
32Epidemics
33Epithelial cells
34Female
35Gene expression
36Gene Expression Profiling - statistics & numerical data
37Gene sequencing
38Genes
39Genetic aspects
40Host-Pathogen Interactions - genetics
41Human tissues
42Humans
43Immunologi inom det medicinska området
44Immunology in the medical area
45Infectious Medicine
46Infektionsmedicin
47Interleukin
48Interleukin 1
49Interleukin 6
50Klinisk medicin
51Lung - metabolism
52Lung - virology
53Lungs
54Macrophages
55Male
56Medical and Health Sciences
57Medicin och hälsovetenskap
58Medicinska och farmaceutiska grundvetenskaper
59Middle Aged
60Organ Specificity - genetics
61Organs
62Parenchyma
63Pathogenesis
64Pathways
65Peptidyl-dipeptidase A
66Quorum sensing
67Respiration
68Respiratory diseases
69Respiratory System - metabolism
70Respiratory System - virology
71Respiratory tract
72Ribonucleic acid
73RNA
74SARS-CoV-2 - physiology
75Sequence Analysis, RNA - methods
76Sequence Analysis, RNA - statistics & numerical data
77Serine Endopeptidases - genetics
78Serine Endopeptidases - metabolism
79Severe acute respiratory syndrome
80Severe acute respiratory syndrome coronavirus 2
81Sex
82Single-Cell Analysis - methods
83Single-Cell Analysis - statistics & numerical data
84Smoking
85Tissues
86Transcriptomics
87Tropism
88United States
89Viral diseases
90Virus Internalization
toplevelpeer_reviewed
creatorcontrib
0Muus, Christoph
1Luecken, Malte D
2Eraslan, Gökcen
3Sikkema, Lisa
4Waghray, Avinash
5Heimberg, Graham
6Kobayashi, Yoshihiko
7Vaishnav, Eeshit Dhaval
8Subramanian, Ayshwarya
9Smillie, Christopher
10Jagadeesh, Karthik A
11Duong, Elizabeth Thu
12Fiskin, Evgenij
13Triglia, Elena Torlai
14Ansari, Meshal
15Cai, Peiwen
16Lin, Brian
17Buchanan, Justin
18Chen, Sijia
19Shu, Jian
20Haber, Adam L
21Chung, Hattie
22Montoro, Daniel T
23Adams, Taylor
24Aliee, Hananeh
25Allon, Samuel J
26Anusivova, Zaneta
27Angelidis, Ilias
28Ashenberg, Orr
29Bassler, Kevin
30Bécavin, Christophe
31Benhar, Inbal
32Bergenstråhle, Joseph
33Bergenstråhle, Ludvig
34Bolt, Liam
35Braun, Emelie
36Bui, Linh T
37Callori, Steven
38Chaffin, Mark
39Chichelnitskiy, Evgeny
40Chiou, Joshua
41Conlon, Thomas M
42Cuoco, Michael S
43Cuomo, Anna S E
44Deprez, Marie
45Duclos, Grant
46Fine, Denise
47Fischer, David S
48Hu, Yan
49Qi, CanCan
50NHLBI LungMap Consortium
51Human Cell Atlas Lung Biological Network
52The Human Cell Atlas Lung Biological Network
53The NHLBI LungMap Consortium
collection
0NARCIS
1NARCIS: Datasets
2Narcis: Open Access
3NARCIS:Publications
4Medline
5MEDLINE
6MEDLINE (Ovid)
7MEDLINE
8MEDLINE
9PubMed
10CrossRef
11Gale General OneFile (A&I only)
12ProQuest Central (Corporate)
13Animal Behavior Abstracts
14Bacteriology Abstracts (Microbiology B)
15Calcium & Calcified Tissue Abstracts
16Chemoreception Abstracts
17Immunology Abstracts
18Neurosciences Abstracts
19Nucleic Acids Abstracts
20Oncogenes and Growth Factors Abstracts
21Toxicology Abstracts
22Virology and AIDS Abstracts
23Health & Medical Collection
24ProQuest Central (purchase pre-March 2016)
25Biology Database (Alumni Edition)
26Medical Database (Alumni Edition)
27Science Database (Alumni Edition)
28ProQuest Pharma Collection
29Technology Research Database
30ProQuest SciTech Collection
31ProQuest Natural Science Collection
32Hospital Premium Collection
33Hospital Premium Collection (Alumni Edition)
34ProQuest Central (Alumni) (purchase pre-March 2016)
35Research Library (Alumni Edition)
36ProQuest Central (Alumni Edition)
37ProQuest Central Essentials
38Biological Science Collection
39ProQuest Central
40Natural Science Collection
41Environmental Sciences and Pollution Management
42ProQuest Central Korea
43Engineering Research Database
44Health Research Premium Collection
45Health Research Premium Collection (Alumni)
46ProQuest Central Student
47Research Library Prep
48AIDS and Cancer Research Abstracts
49SciTech Premium Collection
50ProQuest Health & Medical Complete (Alumni)
51ProQuest Biological Science Collection
52Health & Medical Collection (Alumni Edition)
53Medical Database
54Research Library
55Science Database
56Algology Mycology and Protozoology Abstracts (Microbiology C)
57Biological Science Database
58Research Library (Corporate)
59Biotechnology and BioEngineering Abstracts
60Research Library China
61ProQuest One Academic Eastern Edition
62ProQuest One Academic
63ProQuest One Academic UKI Edition
64ProQuest Central China
65ProQuest Central Basic
66Genetics Abstracts
67SwePub
68SwePub Articles
69SWEPUB Freely available online
jtitleNature medicine
delivery
delcategoryRemote Search Resource
fulltextno_fulltext
addata
au
0Muus, Christoph
1Luecken, Malte D
2Eraslan, Gökcen
3Sikkema, Lisa
4Waghray, Avinash
5Heimberg, Graham
6Kobayashi, Yoshihiko
7Vaishnav, Eeshit Dhaval
8Subramanian, Ayshwarya
9Smillie, Christopher
10Jagadeesh, Karthik A
11Duong, Elizabeth Thu
12Fiskin, Evgenij
13Triglia, Elena Torlai
14Ansari, Meshal
15Cai, Peiwen
16Lin, Brian
17Buchanan, Justin
18Chen, Sijia
19Shu, Jian
20Haber, Adam L
21Chung, Hattie
22Montoro, Daniel T
23Adams, Taylor
24Aliee, Hananeh
25Allon, Samuel J
26Anusivova, Zaneta
27Angelidis, Ilias
28Ashenberg, Orr
29Bassler, Kevin
30Bécavin, Christophe
31Benhar, Inbal
32Bergenstråhle, Joseph
33Bergenstråhle, Ludvig
34Bolt, Liam
35Braun, Emelie
36Bui, Linh T
37Callori, Steven
38Chaffin, Mark
39Chichelnitskiy, Evgeny
40Chiou, Joshua
41Conlon, Thomas M
42Cuoco, Michael S
43Cuomo, Anna S E
44Deprez, Marie
45Duclos, Grant
46Fine, Denise
47Fischer, David S
48Hu, Yan
49Qi, CanCan
aucorp
0NHLBI LungMap Consortium
1Human Cell Atlas Lung Biological Network
2The Human Cell Atlas Lung Biological Network
3The NHLBI LungMap Consortium
formatjournal
genrearticle
ristypeJOUR
atitleSingle-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics
jtitleNature medicine
addtitleNat Med
date2021-03
risdate2021
volume27
issue3
spage546
epage559
pages546-559
issn
01078-8956
11546-170X
eissn1546-170X
abstractAngiotensin-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.
copUnited States
pubNature Publishing Group
pmid33654293
doi10.1038/s41591-020-01227-z
tpages14
orcidid
0https://orcid.org/0000-0003-3720-8051
1https://orcid.org/0000-0002-4134-7612
2https://orcid.org/0000-0002-6059-0116
3https://orcid.org/0000-0001-7122-4448
4https://orcid.org/0000-0001-9686-6295
5https://orcid.org/0000-0002-8819-7965
6https://orcid.org/0000-0002-8851-3534
7https://orcid.org/0000-0001-7464-7921
8https://orcid.org/0000-0003-2779-0893
9https://orcid.org/0000-0003-3293-3158
oafree_for_read