@article {1586137,
	title = {Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics},
	journal = {Nat Med},
	volume = {27},
	number = {3},
	year = {2021},
	month = {2021 03},
	pages = {546-559},
	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 ACE2TMPRSS2 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.},
	keywords = {Adult, Aged, Aged, 80 and over, Alveolar Epithelial Cells, Angiotensin-Converting Enzyme 2, Cathepsin L, COVID-19, Datasets as Topic, Demography, Female, Gene Expression Profiling, Host-Pathogen Interactions, Humans, Lung, Male, Middle Aged, Organ Specificity, Respiratory System, SARS-CoV-2, Sequence Analysis, RNA, Serine Endopeptidases, Single-Cell Analysis, Virus Internalization},
	issn = {1546-170X},
	doi = {10.1038/s41591-020-01227-z},
	author = {Muus, Christoph and Luecken, Malte D and Eraslan, G{\"o}kcen and Sikkema, Lisa and Waghray, Avinash and Heimberg, Graham and Kobayashi, Yoshihiko and Vaishnav, Eeshit Dhaval and Subramanian, Ayshwarya and Smillie, Christopher and Jagadeesh, Karthik A and Duong, Elizabeth Thu and Fiskin, Evgenij and Triglia, Elena Torlai and Ansari, Meshal and Cai, Peiwen and Lin, Brian and Buchanan, Justin and Chen, Sijia and Jian Shu and Haber, Adam L and Chung, Hattie and Montoro, Daniel T and Adams, Taylor and Aliee, Hananeh and Allon, Samuel J and Andrusivova, Zaneta and Angelidis, Ilias and Ashenberg, Orr and Bassler, Kevin and B{\'e}cavin, Christophe and Benhar, Inbal and Bergenstr{\r a}hle, Joseph and Bergenstr{\r a}hle, Ludvig and Bolt, Liam and Braun, Emelie and Bui, Linh T and Callori, Steven and Chaffin, Mark and Chichelnitskiy, Evgeny and Chiou, Joshua and Conlon, Thomas M and Cuoco, Michael S and Cuomo, Anna S E and Deprez, Marie and Duclos, Grant and Fine, Denise and Fischer, David S and Ghazanfar, Shila and Gillich, Astrid and Giotti, Bruno and Gould, Joshua and Guo, Minzhe and Gutierrez, Austin J and Habermann, Arun C and Harvey, Tyler and He, Peng and Hou, Xiaomeng and Hu, Lijuan and Hu, Yan and Jaiswal, Alok and Ji, Lu and Jiang, Peiyong and Kapellos, Theodoros S and Kuo, Christin S and Larsson, Ludvig and Leney-Greene, Michael A and Lim, Kyungtae and Litvi{\v n}ukov{\'a}, Monika and Ludwig, Leif S and Lukassen, Soeren and Luo, Wendy and Maatz, Henrike and Madissoon, Elo and Mamanova, Lira and Manakongtreecheep, Kasidet and Leroy, Sylvie and Mayr, Christoph H and Mbano, Ian M and McAdams, Alexi M and Nabhan, Ahmad N and Nyquist, Sarah K and Penland, Lolita and Poirion, Olivier B and Poli, Sergio and Qi, CanCan and Queen, Rachel and Reichart, Daniel and Rosas, Ivan and Schupp, Jonas C and Shea, Conor V and Shi, Xingyi and Sinha, Rahul and Sit, Rene V and Slowikowski, Kamil and Slyper, Michal and Smith, Neal P and Sountoulidis, Alex and Strunz, Maximilian and Sullivan, Travis B and Sun, Dawei and Talavera-L{\'o}pez, Carlos and Tan, Peng and Tantivit, Jessica and Travaglini, Kyle J and Tucker, Nathan R and Vernon, Katherine A and Wadsworth, Marc H and Waldman, Julia and Wang, Xiuting and Xu, Ke and Yan, Wenjun and Zhao, William and Ziegler, Carly G K and NHLBI LungMap Consortium and Human Cell Atlas Lung Biological Network}
}
