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3 results on '"Slowikowski K"'

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

Author

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, 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, and Ziegler CGK

Subjects
Adult, Aged, Aged, 80 and over, Alveolar Epithelial Cells metabolism, Alveolar Epithelial Cells virology, Angiotensin-Converting Enzyme 2 genetics, Angiotensin-Converting Enzyme 2 metabolism, COVID-19 pathology, COVID-19 virology, Cathepsin L genetics, Cathepsin L metabolism, Datasets as Topic statistics & numerical data, Demography, Female, Gene Expression Profiling statistics & numerical data, Humans, Lung metabolism, Lung virology, Male, Middle Aged, Organ Specificity genetics, Respiratory System metabolism, Respiratory System virology, Sequence Analysis, RNA methods, Serine Endopeptidases genetics, Serine Endopeptidases metabolism, Single-Cell Analysis methods, COVID-19 epidemiology, COVID-19 genetics, Host-Pathogen Interactions genetics, SARS-CoV-2 physiology, Sequence Analysis, RNA statistics & numerical data, Single-Cell Analysis statistics & numerical data, Virus Internalization
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.

Published
2021
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2. Common genetic variants modulate pathogen-sensing responses in human dendritic cells.

Author

Lee MN, Ye C, Villani AC, Raj T, Li W, Eisenhaure TM, Imboywa SH, Chipendo PI, Ran FA, Slowikowski K, Ward LD, Raddassi K, McCabe C, Lee MH, Frohlich IY, Hafler DA, Kellis M, Raychaudhuri S, Zhang F, Stranger BE, Benoist CO, De Jager PL, Regev A, and Hacohen N

Subjects
Adult, Autoimmune Diseases genetics, Communicable Diseases genetics, Dendritic Cells drug effects, Escherichia coli, Female, Genetic Loci, Genome-Wide Association Study, HEK293 Cells, Humans, Influenza A virus, Interferon-beta pharmacology, Lipopolysaccharides immunology, Male, Middle Aged, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Transcriptome, Young Adult, Dendritic Cells immunology, Gene-Environment Interaction, Host-Pathogen Interactions genetics, Interferon Regulatory Factor-7 genetics, STAT Transcription Factors genetics
Abstract

Little is known about how human genetic variation affects the responses to environmental stimuli in the context of complex diseases. Experimental and computational approaches were applied to determine the effects of genetic variation on the induction of pathogen-responsive genes in human dendritic cells. We identified 121 common genetic variants associated in cis with variation in expression responses to Escherichia coli lipopolysaccharide, influenza, or interferon-β (IFN-β). We localized and validated causal variants to binding sites of pathogen-activated STAT (signal transducer and activator of transcription) and IRF (IFN-regulatory factor) transcription factors. We also identified a common variant in IRF7 that is associated in trans with type I IFN induction in response to influenza infection. Our results reveal common alleles that explain interindividual variation in pathogen sensing and provide functional annotation for genetic variants that alter susceptibility to inflammatory diseases.

Published
2014
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3. Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics

Author

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, and Human Cell Atlas Lung Biological Network

Subjects
Adult, Male, Cathepsin L, Immunology, Respiratory System, Datasets as Topic, Humans, Lung, 11 Medical and Health Sciences, Aged, Demography, Aged, 80 and over, SARS-CoV-2, Sequence Analysis, RNA, Gene Expression Profiling, Serine Endopeptidases, COVID-19, respiratory system, Middle Aged, Virus Internalization, Organ Specificity, Alveolar Epithelial Cells, Host-Pathogen Interactions, Female, Angiotensin-Converting Enzyme 2, Single-Cell Analysis
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.

Published
2020

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