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Smoking modulates different secretory subpopulations expressing SARS-CoV-2 entry genes in the nasal and bronchial airways

SARS-CoV-2 infection and disease severity are influenced by viral entry (VE) gene expression patterns in the airway epithelium. The similarities and differences of VE gene expression (ACE2, TMPRSS2, and CTSL) across nasal and bronchial compartments have not been fully characterized using matched sam...

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Autores principales: Xu, Ke, Shi, Xingyi, Husted, Christopher, Hong, Rui, Wang, Yichen, Ning, Boting, Sullivan, Travis B., Rieger-Christ, Kimberly M., Duan, Fenghai, Marques, Helga, Gower, Adam C., Xiao, Xiaohui, Liu, Hanqiao, Liu, Gang, Duclos, Grant, Platt, Michael, Spira, Avrum E., Mazzilli, Sarah A., Billatos, Ehab, Lenburg, Marc E., Campbell, Joshua D., Beane, Jennifer E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9615627/
https://www.ncbi.nlm.nih.gov/pubmed/36307504
http://dx.doi.org/10.1038/s41598-022-17832-6
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author Xu, Ke
Shi, Xingyi
Husted, Christopher
Hong, Rui
Wang, Yichen
Ning, Boting
Sullivan, Travis B.
Rieger-Christ, Kimberly M.
Duan, Fenghai
Marques, Helga
Gower, Adam C.
Xiao, Xiaohui
Liu, Hanqiao
Liu, Gang
Duclos, Grant
Platt, Michael
Spira, Avrum E.
Mazzilli, Sarah A.
Billatos, Ehab
Lenburg, Marc E.
Campbell, Joshua D.
Beane, Jennifer E.
author_facet Xu, Ke
Shi, Xingyi
Husted, Christopher
Hong, Rui
Wang, Yichen
Ning, Boting
Sullivan, Travis B.
Rieger-Christ, Kimberly M.
Duan, Fenghai
Marques, Helga
Gower, Adam C.
Xiao, Xiaohui
Liu, Hanqiao
Liu, Gang
Duclos, Grant
Platt, Michael
Spira, Avrum E.
Mazzilli, Sarah A.
Billatos, Ehab
Lenburg, Marc E.
Campbell, Joshua D.
Beane, Jennifer E.
author_sort Xu, Ke
collection PubMed
description SARS-CoV-2 infection and disease severity are influenced by viral entry (VE) gene expression patterns in the airway epithelium. The similarities and differences of VE gene expression (ACE2, TMPRSS2, and CTSL) across nasal and bronchial compartments have not been fully characterized using matched samples from large cohorts. Gene expression data from 793 nasal and 1673 bronchial brushes obtained from individuals participating in lung cancer screening or diagnostic workup revealed that smoking status (current versus former) was the only clinical factor significantly and reproducibly associated with VE gene expression. The expression of ACE2 and TMPRSS2 was higher in smokers in the bronchus but not in the nose. scRNA-seq of nasal brushings indicated that ACE2 co-expressed genes were highly expressed in club and C15orf48(+) secretory cells while TMPRSS2 co-expressed genes were highly expressed in keratinizing epithelial cells. In contrast, these ACE2 and TMPRSS2 modules were highly expressed in goblet cells in scRNA-seq from bronchial brushings. Cell-type deconvolution of the gene expression data confirmed that smoking increased the abundance of several secretory cell populations in the bronchus, but only goblet cells in the nose. The association of ACE2 and TMPRSS2 with smoking in the bronchus is due to their high expression in goblet cells which increase in abundance in current smoker airways. In contrast, in the nose, these genes are not predominantly expressed in cell populations modulated by smoking. In individuals with elevated lung cancer risk, smoking-induced VE gene expression changes in the nose likely have minimal impact on SARS-CoV-2 infection, but in the bronchus, smoking may lead to higher viral loads and more severe disease.
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spelling pubmed-96156272022-10-28 Smoking modulates different secretory subpopulations expressing SARS-CoV-2 entry genes in the nasal and bronchial airways Xu, Ke Shi, Xingyi Husted, Christopher Hong, Rui Wang, Yichen Ning, Boting Sullivan, Travis B. Rieger-Christ, Kimberly M. Duan, Fenghai Marques, Helga Gower, Adam C. Xiao, Xiaohui Liu, Hanqiao Liu, Gang Duclos, Grant Platt, Michael Spira, Avrum E. Mazzilli, Sarah A. Billatos, Ehab Lenburg, Marc E. Campbell, Joshua D. Beane, Jennifer E. Sci Rep Article SARS-CoV-2 infection and disease severity are influenced by viral entry (VE) gene expression patterns in the airway epithelium. The similarities and differences of VE gene expression (ACE2, TMPRSS2, and CTSL) across nasal and bronchial compartments have not been fully characterized using matched samples from large cohorts. Gene expression data from 793 nasal and 1673 bronchial brushes obtained from individuals participating in lung cancer screening or diagnostic workup revealed that smoking status (current versus former) was the only clinical factor significantly and reproducibly associated with VE gene expression. The expression of ACE2 and TMPRSS2 was higher in smokers in the bronchus but not in the nose. scRNA-seq of nasal brushings indicated that ACE2 co-expressed genes were highly expressed in club and C15orf48(+) secretory cells while TMPRSS2 co-expressed genes were highly expressed in keratinizing epithelial cells. In contrast, these ACE2 and TMPRSS2 modules were highly expressed in goblet cells in scRNA-seq from bronchial brushings. Cell-type deconvolution of the gene expression data confirmed that smoking increased the abundance of several secretory cell populations in the bronchus, but only goblet cells in the nose. The association of ACE2 and TMPRSS2 with smoking in the bronchus is due to their high expression in goblet cells which increase in abundance in current smoker airways. In contrast, in the nose, these genes are not predominantly expressed in cell populations modulated by smoking. In individuals with elevated lung cancer risk, smoking-induced VE gene expression changes in the nose likely have minimal impact on SARS-CoV-2 infection, but in the bronchus, smoking may lead to higher viral loads and more severe disease. Nature Publishing Group UK 2022-10-28 /pmc/articles/PMC9615627/ /pubmed/36307504 http://dx.doi.org/10.1038/s41598-022-17832-6 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Xu, Ke
Shi, Xingyi
Husted, Christopher
Hong, Rui
Wang, Yichen
Ning, Boting
Sullivan, Travis B.
Rieger-Christ, Kimberly M.
Duan, Fenghai
Marques, Helga
Gower, Adam C.
Xiao, Xiaohui
Liu, Hanqiao
Liu, Gang
Duclos, Grant
Platt, Michael
Spira, Avrum E.
Mazzilli, Sarah A.
Billatos, Ehab
Lenburg, Marc E.
Campbell, Joshua D.
Beane, Jennifer E.
Smoking modulates different secretory subpopulations expressing SARS-CoV-2 entry genes in the nasal and bronchial airways
title Smoking modulates different secretory subpopulations expressing SARS-CoV-2 entry genes in the nasal and bronchial airways
title_full Smoking modulates different secretory subpopulations expressing SARS-CoV-2 entry genes in the nasal and bronchial airways
title_fullStr Smoking modulates different secretory subpopulations expressing SARS-CoV-2 entry genes in the nasal and bronchial airways
title_full_unstemmed Smoking modulates different secretory subpopulations expressing SARS-CoV-2 entry genes in the nasal and bronchial airways
title_short Smoking modulates different secretory subpopulations expressing SARS-CoV-2 entry genes in the nasal and bronchial airways
title_sort smoking modulates different secretory subpopulations expressing sars-cov-2 entry genes in the nasal and bronchial airways
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9615627/
https://www.ncbi.nlm.nih.gov/pubmed/36307504
http://dx.doi.org/10.1038/s41598-022-17832-6
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