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

Muus, C; Luecken, MD; Eraslan, G; Sikkema, L; Waghray, A; Heimberg, G; Kobayashi, Y; Vaishnav, ED; Subramanian, A; Smillie, C; Jagadeesh, KA; Duong, ET; Fiskin, E; Triglia, ET; Ansari, M; Cai, P; Lin, B; Buchanan, J; Chen, S; Shu, J; Haber, AL; Chung, H; Montoro, DT; Adams, T; Aliee, H; Allon, SJ; Andrusivova, Z; Angelidis, I; Ashenberg, O; Bassler, K; Bécavin, C; Benhar, I; Bergenstråhle, J; Bergenstråhle, L; Bolt, L; Braun, E; Bui, LT; Callori, S; Chaffin, M; Chichelnitskiy, E; Chiou, J; Conlon, TM; Cuoco, MS; Cuomo, ASE; Deprez, M; Duclos, G; Fine, D; Fischer, DS; Ghazanfar, S; Gillich, A; Giotti, B; Gould, J; Guo, M; Gutierrez, AJ; Habermann, AC; Harvey, T; He, P; Hou, X; Hu, L; Hu, Y; Jaiswal, A; Ji, L; Jiang, P; Kapellos, TS; Kuo, CS; Larsson, L; Leney-Greene, MA; Lim, K; Litviňuková, M; Ludwig, LS; Lukassen, S; Luo, W; Maatz, H; Madissoon, E; Mamanova, L; Manakongtreecheep, K; Leroy, S; Mayr, CH; Mbano, IM; McAdams, AM; Nabhan, AN; Nyquist, SK; Penland, L; Poirion, OB; Poli, S; Qi, C; Queen, R; Reichart, D; Rosas, I; Schupp, JC; Shea, CV; Shi, X; Sinha, R; Sit, RV; Slowikowski, K; Slyper, M; Smith, NP; Sountoulidis, A; Strunz, M; Sullivan, TB; Sun, D; Talavera-López, C; Tan, P; Tantivit, J; Travaglini, KJ; Tucker, NR; Vernon, KA; Wadsworth, MH; Waldman, J; Wang, X; Xu, K; Yan, W; Zhao, W; Ziegler, CGK; NHLBI LungMap Consortium,; Human Cell Atlas Lung Biological Network,

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

Muus, C Luecken, MD Eraslan, G Sikkema, L Waghray, A Heimberg, G Kobayashi, Y Vaishnav, ED Subramanian, A Smillie, C Jagadeesh, KA Duong, ET Fiskin, E Triglia, ET Ansari, M Cai, P Lin, B Buchanan, J Chen, S Shu, J Haber, AL Chung, H Montoro, DT Adams, T Aliee, H Allon, SJ Andrusivova, Z Angelidis, I Ashenberg, O Bassler, K Bécavin, C Benhar, I Bergenstråhle, J Bergenstråhle, L Bolt, L Braun, E Bui, LT Callori, S Chaffin, M Chichelnitskiy, E Chiou, J Conlon, TM Cuoco, MS Cuomo, ASE Deprez, M Duclos, G Fine, D Fischer, DS Ghazanfar, S Gillich, A Giotti, B Gould, J Guo, M Gutierrez, AJ Habermann, AC Harvey, T He, P Hou, X Hu, L Hu, Y Jaiswal, A Ji, L Jiang, P Kapellos, TS Kuo, CS Larsson, L Leney-Greene, MA Lim, K Litviňuková, M Ludwig, LS Lukassen, S Luo, W Maatz, H Madissoon, E Mamanova, L Manakongtreecheep, K Leroy, S Mayr, CH Mbano, IM McAdams, AM Nabhan, AN Nyquist, SK Penland, L Poirion, OB Poli, S Qi, C Queen, R Reichart, D Rosas, I Schupp, JC Shea, CV Shi, X Sinha, R Sit, RV Slowikowski, K Slyper, M Smith, NP Sountoulidis, A Strunz, M Sullivan, TB Sun, D Talavera-López, C Tan, P Tantivit, J Travaglini, KJ Tucker, NR Vernon, KA Wadsworth, MH Waldman, J Wang, X Xu, K Yan, W Zhao, W Ziegler, CGK NHLBI LungMap Consortium, Human Cell Atlas Lung Biological Network,

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Publisher:: Nature Research
Publication Type:: Journal Article
Citation:: Nature Medicine, 2021, 27, (3), pp. 546-559
Issue Date:: 2021-03

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Field	Value	Language
dc.contributor.author	Muus, C
dc.contributor.author	Luecken, MD
dc.contributor.author	Eraslan, G
dc.contributor.author	Sikkema, L
dc.contributor.author	Waghray, A
dc.contributor.author	Heimberg, G
dc.contributor.author	Kobayashi, Y
dc.contributor.author	Vaishnav, ED
dc.contributor.author	Subramanian, A
dc.contributor.author	Smillie, C
dc.contributor.author	Jagadeesh, KA
dc.contributor.author	Duong, ET
dc.contributor.author	Fiskin, E
dc.contributor.author	Triglia, ET
dc.contributor.author	Ansari, M
dc.contributor.author	Cai, P
dc.contributor.author	Lin, B
dc.contributor.author	Buchanan, J
dc.contributor.author	Chen, S
dc.contributor.author	Shu, J
dc.contributor.author	Haber, AL
dc.contributor.author	Chung, H
dc.contributor.author	Montoro, DT
dc.contributor.author	Adams, T
dc.contributor.author	Aliee, H
dc.contributor.author	Allon, SJ
dc.contributor.author	Andrusivova, Z
dc.contributor.author	Angelidis, I
dc.contributor.author	Ashenberg, O
dc.contributor.author	Bassler, K
dc.contributor.author	Bécavin, C
dc.contributor.author	Benhar, I
dc.contributor.author	Bergenstråhle, J
dc.contributor.author	Bergenstråhle, L
dc.contributor.author	Bolt, L
dc.contributor.author	Braun, E
dc.contributor.author	Bui, LT
dc.contributor.author	Callori, S
dc.contributor.author	Chaffin, M
dc.contributor.author	Chichelnitskiy, E
dc.contributor.author	Chiou, J
dc.contributor.author	Conlon, TM
dc.contributor.author	Cuoco, MS
dc.contributor.author	Cuomo, ASE
dc.contributor.author	Deprez, M
dc.contributor.author	Duclos, G
dc.contributor.author	Fine, D
dc.contributor.author	Fischer, DS
dc.contributor.author	Ghazanfar, S
dc.contributor.author	Gillich, A
dc.contributor.author	Giotti, B
dc.contributor.author	Gould, J
dc.contributor.author	Guo, M
dc.contributor.author	Gutierrez, AJ
dc.contributor.author	Habermann, AC
dc.contributor.author	Harvey, T
dc.contributor.author	He, P
dc.contributor.author	Hou, X
dc.contributor.author	Hu, L
dc.contributor.author	Hu, Y
dc.contributor.author	Jaiswal, A
dc.contributor.author	Ji, L
dc.contributor.author	Jiang, P
dc.contributor.author	Kapellos, TS
dc.contributor.author	Kuo, CS
dc.contributor.author	Larsson, L
dc.contributor.author	Leney-Greene, MA
dc.contributor.author	Lim, K
dc.contributor.author	Litviňuková, M
dc.contributor.author	Ludwig, LS
dc.contributor.author	Lukassen, S
dc.contributor.author	Luo, W
dc.contributor.author	Maatz, H
dc.contributor.author	Madissoon, E
dc.contributor.author	Mamanova, L
dc.contributor.author	Manakongtreecheep, K
dc.contributor.author	Leroy, S
dc.contributor.author	Mayr, CH
dc.contributor.author	Mbano, IM
dc.contributor.author	McAdams, AM
dc.contributor.author	Nabhan, AN
dc.contributor.author	Nyquist, SK
dc.contributor.author	Penland, L
dc.contributor.author	Poirion, OB
dc.contributor.author	Poli, S
dc.contributor.author	Qi, C
dc.contributor.author	Queen, R
dc.contributor.author	Reichart, D
dc.contributor.author	Rosas, I
dc.contributor.author	Schupp, JC
dc.contributor.author	Shea, CV
dc.contributor.author	Shi, X
dc.contributor.author	Sinha, R
dc.contributor.author	Sit, RV
dc.contributor.author	Slowikowski, K
dc.contributor.author	Slyper, M
dc.contributor.author	Smith, NP
dc.contributor.author	Sountoulidis, A
dc.contributor.author	Strunz, M
dc.contributor.author	Sullivan, TB
dc.contributor.author	Sun, D
dc.contributor.author	Talavera-López, C
dc.contributor.author	Tan, P
dc.contributor.author	Tantivit, J
dc.contributor.author	Travaglini, KJ
dc.contributor.author	Tucker, NR
dc.contributor.author	Vernon, KA
dc.contributor.author	Wadsworth, MH
dc.contributor.author	Waldman, J
dc.contributor.author	Wang, X
dc.contributor.author	Xu, K
dc.contributor.author	Yan, W
dc.contributor.author	Zhao, W
dc.contributor.author	Ziegler, CGK
dc.contributor.author	NHLBI LungMap Consortium,
dc.contributor.author	Human Cell Atlas Lung Biological Network,
dc.date.accessioned	2022-01-11T04:59:21Z
dc.date.available	2020-12-23
dc.date.available	2022-01-11T04:59:21Z
dc.date.issued	2021-03
dc.identifier.citation	Nature Medicine, 2021, 27, (3), pp. 546-559
dc.identifier.issn	1078-8956
dc.identifier.issn	1546-170X
dc.identifier.uri	http://hdl.handle.net/10453/152907
dc.description.abstract	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.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	Nature Research
dc.relation.ispartof	Nature Medicine
dc.relation.isbasedon	10.1038/s41591-020-01227-z
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	11 Medical and Health Sciences
dc.subject.classification	Immunology
dc.subject.mesh	Adult
dc.subject.mesh	Aged
dc.subject.mesh	Aged, 80 and over
dc.subject.mesh	Alveolar Epithelial Cells
dc.subject.mesh	Angiotensin-Converting Enzyme 2
dc.subject.mesh	Cathepsin L
dc.subject.mesh	COVID-19
dc.subject.mesh	Datasets as Topic
dc.subject.mesh	Demography
dc.subject.mesh	Female
dc.subject.mesh	Gene Expression Profiling
dc.subject.mesh	Host-Pathogen Interactions
dc.subject.mesh	Humans
dc.subject.mesh	Lung
dc.subject.mesh	Male
dc.subject.mesh	Middle Aged
dc.subject.mesh	Organ Specificity
dc.subject.mesh	Respiratory System
dc.subject.mesh	SARS-CoV-2
dc.subject.mesh	Sequence Analysis, RNA
dc.subject.mesh	Serine Endopeptidases
dc.subject.mesh	Single-Cell Analysis
dc.subject.mesh	Virus Internalization
dc.subject.mesh	Adult
dc.subject.mesh	Aged
dc.subject.mesh	Aged, 80 and over
dc.subject.mesh	Alveolar Epithelial Cells
dc.subject.mesh	Angiotensin-Converting Enzyme 2
dc.subject.mesh	COVID-19
dc.subject.mesh	Cathepsin L
dc.subject.mesh	Datasets as Topic
dc.subject.mesh	Demography
dc.subject.mesh	Female
dc.subject.mesh	Gene Expression Profiling
dc.subject.mesh	Host-Pathogen Interactions
dc.subject.mesh	Humans
dc.subject.mesh	Lung
dc.subject.mesh	Male
dc.subject.mesh	Middle Aged
dc.subject.mesh	Organ Specificity
dc.subject.mesh	Respiratory System
dc.subject.mesh	SARS-CoV-2
dc.subject.mesh	Sequence Analysis, RNA
dc.subject.mesh	Serine Endopeptidases
dc.subject.mesh	Single-Cell Analysis
dc.subject.mesh	Virus Internalization
dc.subject.mesh	Respiratory System
dc.subject.mesh	Lung
dc.subject.mesh	Humans
dc.subject.mesh	Serine Endopeptidases
dc.subject.mesh	Gene Expression Profiling
dc.subject.mesh	Sequence Analysis, RNA
dc.subject.mesh	Demography
dc.subject.mesh	Organ Specificity
dc.subject.mesh	Adult
dc.subject.mesh	Aged
dc.subject.mesh	Aged, 80 and over
dc.subject.mesh	Middle Aged
dc.subject.mesh	Female
dc.subject.mesh	Male
dc.subject.mesh	Virus Internalization
dc.subject.mesh	Host-Pathogen Interactions
dc.subject.mesh	Cathepsin L
dc.subject.mesh	Single-Cell Analysis
dc.subject.mesh	Datasets as Topic
dc.subject.mesh	Alveolar Epithelial Cells
dc.subject.mesh	COVID-19
dc.subject.mesh	Angiotensin-Converting Enzyme 2
dc.subject.mesh	SARS-CoV-2
dc.title	Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics.
dc.type	Journal Article
utslib.citation.volume	27
utslib.location.activity	United States
utslib.for	11 Medical and Health Sciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Centre for Health Technologies (CHT)
utslib.copyright.status	closed_access	*
pubs.consider-herdc	false
dc.date.updated	2022-01-11T04:59:14Z
pubs.issue	3
pubs.publication-status	Published
pubs.volume	27
utslib.citation.issue	3

Abstract:

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.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/152907