| Literature DB >> 33654293 |
Christoph Muus1,2, Malte D Luecken3, Gökcen Eraslan4, Lisa Sikkema5, Avinash Waghray6,7,8, Graham Heimberg4, Yoshihiko Kobayashi9, Eeshit Dhaval Vaishnav4,10, Ayshwarya Subramanian4, Christopher Smillie4, Karthik A Jagadeesh4, Elizabeth Thu Duong11, Evgenij Fiskin4, Elena Torlai Triglia4, Meshal Ansari12,13, Peiwen Cai14, Brian Lin7,8,6, Justin Buchanan15,16, Sijia Chen17, Jian Shu18,19, Adam L Haber4,20, Hattie Chung4, Daniel T Montoro4, Taylor Adams21, Hananeh Aliee13, Samuel J Allon18,22,23, Zaneta Andrusivova24, Ilias Angelidis12, Orr Ashenberg4, Kevin Bassler25, Christophe Bécavin26, Inbal Benhar4, Joseph Bergenstråhle24, Ludvig Bergenstråhle24, Liam Bolt27, Emelie Braun28, Linh T Bui29, Steven Callori30,31, Mark Chaffin32, Evgeny Chichelnitskiy33,34, Joshua Chiou35, Thomas M Conlon12, Michael S Cuoco4, Anna S E Cuomo36, Marie Deprez26, Grant Duclos37, Denise Fine38, David S Fischer13,39, Shila Ghazanfar40, Astrid Gillich41, Bruno Giotti42, Joshua Gould4, Minzhe Guo43, Austin J Gutierrez29, Arun C Habermann44, Tyler Harvey4, Peng He27, Xiaomeng Hou45,46, Lijuan Hu28, Yan Hu47, Alok Jaiswal4, Lu Ji48, Peiyong Jiang48, Theodoros S Kapellos49, Christin S Kuo50, Ludvig Larsson51, Michael A Leney-Greene4, Kyungtae Lim52, Monika Litviňuková53,54, Leif S Ludwig4,55, Soeren Lukassen56,57, Wendy Luo4, Henrike Maatz54, Elo Madissoon58,59, Lira Mamanova27, Kasidet Manakongtreecheep18,60,61, Sylvie Leroy62,63, Christoph H Mayr64, Ian M Mbano65,66, Alexi M McAdams67, Ahmad N Nabhan41, Sarah K Nyquist18,23,68, Lolita Penland41, Olivier B Poirion45,46, Sergio Poli21, CanCan Qi69,70, Rachel Queen71, Daniel Reichart72,73, Ivan Rosas21, Jonas C Schupp74, Conor V Shea75, Xingyi Shi75,76, Rahul Sinha77, Rene V Sit41, Kamil Slowikowski18,60,61, Michal Slyper4, Neal P Smith78, Alex Sountoulidis79, Maximilian Strunz80, Travis B Sullivan81, Dawei Sun52, Carlos Talavera-López82, Peng Tan4, Jessica Tantivit18,60,61, Kyle J Travaglini41, Nathan R Tucker32,83, Katherine A Vernon18,84, Marc H Wadsworth18,23,85, Julia Waldman4, Xiuting Wang14, Ke Xu75, Wenjun Yan86,87, William Zhao14, Carly G K Ziegler18,23,88.
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.Entities:
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Year: 2021 PMID： 33654293 PMCID： PMC9469728 DOI： 10.1038/s41591-020-01227-z
Source DB: PubMed Journal: Nat Med ISSN： 1078-8956 Impact factor: 87.241