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10.1038/s41591-020-01227-z

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suck abstract from ncbi


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pmid33654293      Nat+Med 2021 ; 27 (3): 546-559
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  • Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics #MMPMID33654293
  • 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; Torlai Triglia E; 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; Becavin C; Benhar I; Bergenstrahle J; Bergenstrahle 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; Litvinukova 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-Lopez 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
  • Nat Med 2021[Mar]; 27 (3): 546-559 PMID33654293show ga
  • 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.
  • |*Virus Internalization[MESH]
  • |Adult[MESH]
  • |Aged[MESH]
  • |Aged, 80 and over[MESH]
  • |Alveolar Epithelial Cells/metabolism/virology[MESH]
  • |Angiotensin-Converting Enzyme 2/genetics/metabolism[MESH]
  • |COVID-19/*epidemiology/*genetics/pathology/virology[MESH]
  • |Cathepsin L/genetics/metabolism[MESH]
  • |Datasets as Topic/statistics & numerical data[MESH]
  • |Demography[MESH]
  • |Female[MESH]
  • |Gene Expression Profiling/statistics & numerical data[MESH]
  • |Host-Pathogen Interactions/*genetics[MESH]
  • |Humans[MESH]
  • |Lung/metabolism/virology[MESH]
  • |Male[MESH]
  • |Middle Aged[MESH]
  • |Organ Specificity/genetics[MESH]
  • |Respiratory System/metabolism/virology[MESH]
  • |SARS-CoV-2/*physiology[MESH]
  • |Sequence Analysis, RNA/methods/*statistics & numerical data[MESH]
  • |Serine Endopeptidases/genetics/metabolism[MESH]


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