TY - JOUR
T1 - Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics
AU - The NHLBI LungMap Consortium
AU - The Human Cell Atlas Lung Biological Network
AU - Muus, Christoph
AU - Luecken, Malte D.
AU - Eraslan, Gökcen
AU - Sikkema, Lisa
AU - Waghray, Avinash
AU - Heimberg, Graham
AU - Kobayashi, Yoshihiko
AU - Vaishnav, Eeshit Dhaval
AU - Subramanian, Ayshwarya
AU - Smillie, Christopher
AU - Jagadeesh, Karthik A.
AU - Duong, Elizabeth Thu
AU - Fiskin, Evgenij
AU - Triglia, Elena Torlai
AU - Ansari, Meshal
AU - Cai, Peiwen
AU - Lin, Brian
AU - Buchanan, Justin
AU - Chen, Sijia
AU - Shu, Jian
AU - Haber, Adam L.
AU - Chung, Hattie
AU - Montoro, Daniel T.
AU - Adams, Taylor
AU - Aliee, Hananeh
AU - Allon, Samuel J.
AU - Andrusivova, Zaneta
AU - Angelidis, Ilias
AU - Ashenberg, Orr
AU - Bassler, Kevin
AU - Bécavin, Christophe
AU - Benhar, Inbal
AU - Bergenstråhle, Joseph
AU - Bergenstråhle, Ludvig
AU - Bolt, Liam
AU - Braun, Emelie
AU - Bui, Linh T.
AU - Callori, Steven
AU - Chaffin, Mark
AU - Chichelnitskiy, Evgeny
AU - Chiou, Joshua
AU - Conlon, Thomas M.
AU - Cuoco, Michael S.
AU - Cuomo, Anna S.E.
AU - Deprez, Marie
AU - Duclos, Grant
AU - Fine, Denise
AU - Fischer, David S.
AU - Ghazanfar, Shila
AU - Lee, Haeock
N1 - Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2021/3
Y1 - 2021/3
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85102367125
U2 - 10.1038/s41591-020-01227-z
DO - 10.1038/s41591-020-01227-z
M3 - Article
C2 - 33654293
AN - SCOPUS:85102367125
SN - 1078-8956
VL - 27
SP - 546
EP - 559
JO - Nature Medicine
JF - Nature Medicine
IS - 3
ER -