Smoking induces shifts in cellular composition and transcriptome within the bronchial mucus barrier
Respirology, vol. 28, pp. 132–142
Abstract
BACKGROUND AND OBJECTIVE: Smoking disturbs the bronchial-mucus-barrier. This study assesses the cellular composition and gene expression shifts of the bronchial-mucus-barrier with smoking to understand the mechanism of mucosal damage by cigarette smoke exposure. We explore whether single-cell-RNA-sequencing (scRNA-seq) based cellular deconvolution (CD) can predict cell-type composition in RNA-seq data. METHODS: RNA-seq data of bronchial biopsies from three cohorts were analysed using CD. The cohorts included 56 participants with chronic obstructive pulmonary disease [COPD] (38 smokers; 18 ex-smokers), 77 participants without COPD (40 never-smokers; 37 smokers) and 16 participants who stopped smoking for 1 year (11 COPD and 5 non-COPD-smokers). Differential gene expression was used to investigate gene expression shifts. The CD-derived goblet cell ratios were validated by correlating with staining-derived goblet cell ratios from the COPD cohort. Statistics were done in the R software (false discovery rate p-value < 0.05). RESULTS: Both CD methods indicate a shift in bronchial-mucus-barrier cell composition towards goblet cells in COPD and non-COPD-smokers compared to ex- and never-smokers. It shows that the effect was reversible within a year of smoking cessation. A reduction of ciliated and basal cells was observed with current smoking, which resolved following smoking cessation. The expression of mucin and sodium channel (ENaC) genes, but not chloride channel genes, were altered in COPD and current smokers compared to never smokers or ex-smokers. The goblet cell-derived staining scores correlate with CD-derived goblet cell ratios. CONCLUSION: Smoking alters bronchial-mucus-barrier cell composition, transcriptome and increases mucus production. This effect is partly reversible within a year of smoking cessation. CD methodology can predict goblet-cell percentages from RNA-seq.
Authors 14
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University of Technology Sydney · The University of Sydney · Woolcock Institute of Medical Research
Affiliation as printed
The University of Sydney, Respiratory Cellular and Molecular Biology (RCMB), Woolcock Institute of Medical Research Sydney New South Wales Australia
University of Technology Sydney, Respiratory Bioinformatics and Molecular Biology (RBMB), School of Life Sciences Sydney New South Wales Australia
The University of Sydney, Respiratory Cellular and Molecular Biology (RCMB), Woolcock Institute of Medical Research, Sydney, New South Wales, Australia
University of Technology Sydney, Respiratory Bioinformatics and Molecular Biology (RBMB), School of Life Sciences, Sydney, New South Wales, Australia
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University Medical Center Groningen · University of Groningen
Affiliation as printed
Department of Pulmonary Diseases University of Groningen, University Medical Center Groningen Groningen the Netherlands
University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD Groningen the Netherlands
Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD, Groningen, the Netherlands
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University of Technology Sydney · University Medical Center Groningen · University of Groningen
Affiliation as printed
Department of Pathology & Medical Biology University of Groningen, University Medical Center Groningen Groningen the Netherlands
University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD Groningen the Netherlands
University of Technology Sydney, Respiratory Bioinformatics and Molecular Biology (RBMB), School of Life Sciences Sydney New South Wales Australia
Department of Pathology & Medical Biology University of Groningen, University Medical Center Groningen Groningen the Netherlands
University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD, Groningen, the Netherlands
University of Technology Sydney, Respiratory Bioinformatics and Molecular Biology (RBMB), School of Life Sciences, Sydney, New South Wales, Australia
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University of Technology Sydney · Centenary Institute
Affiliation as printed
Centre for Inflammation Centenary Institute, and the University of Technology Sydney, Faculty of Science Sydney New South Wales Australia
University of Technology Sydney, Respiratory Bioinformatics and Molecular Biology (RBMB), School of Life Sciences Sydney New South Wales Australia
Centre for Inflammation, Centenary Institute, and the University of Technology Sydney, Faculty of Science, Sydney, New South Wales, Australia
University of Technology Sydney, Respiratory Bioinformatics and Molecular Biology (RBMB), School of Life Sciences, Sydney, New South Wales, Australia
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University of Technology Sydney · Centenary Institute
Affiliation as printed
Centre for Inflammation Centenary Institute, and the University of Technology Sydney, Faculty of Science Sydney New South Wales Australia
Centre for Inflammation, Centenary Institute, and the University of Technology Sydney, Faculty of Science, Sydney, New South Wales, Australia
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University Medical Center Groningen · University of Groningen
Affiliation as printed
Department of Pathology & Medical Biology University of Groningen, University Medical Center Groningen Groningen the Netherlands
University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD Groningen the Netherlands
Department of Pathology & Medical Biology University of Groningen, University Medical Center Groningen Groningen the Netherlands
University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD, Groningen, the Netherlands
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University Medical Center Groningen · University of Groningen
Affiliation as printed
Department of Pathology & Medical Biology University of Groningen, University Medical Center Groningen Groningen the Netherlands
University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD Groningen the Netherlands
Department of Pathology & Medical Biology University of Groningen, University Medical Center Groningen Groningen the Netherlands
University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD, Groningen, the Netherlands
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Annemarie M. van Schadewijk Aachen Department of Pulmonology Leiden University Medical Center Leiden The Netherlands Dept of Pulmonology, Leiden University Medical Center
Leiden University Medical Center
Affiliation as printed
Department of Pulmonology Leiden University Medical Center Leiden the Netherlands
Department of Pulmonology, Leiden University Medical Center, Leiden, the Netherlands
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Pieter Sicco Hiemstra Aachen Department of Pulmonology Leiden University Medical Center Leiden The Netherlands Dept of Pulmonology, Leiden University Medical Center
Leiden University Medical Center
Affiliation as printed
Department of Pulmonology Leiden University Medical Center Leiden the Netherlands
Department of Pulmonology, Leiden University Medical Center, Leiden, the Netherlands
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University Medical Center Groningen · University of Groningen
Affiliation as printed
Department of Pulmonary Diseases University of Groningen, University Medical Center Groningen Groningen the Netherlands
University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD Groningen the Netherlands
Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD, Groningen, the Netherlands
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The University of Sydney · Woolcock Institute of Medical Research
Affiliation as printed
The University of Sydney, Respiratory Cellular and Molecular Biology (RCMB), Woolcock Institute of Medical Research Sydney New South Wales Australia
The University of Sydney, Respiratory Cellular and Molecular Biology (RCMB), Woolcock Institute of Medical Research, Sydney, New South Wales, Australia
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University Medical Center Groningen · University of Groningen
Affiliation as printed
Department of Pulmonary Diseases University of Groningen, University Medical Center Groningen Groningen the Netherlands
University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD Groningen the Netherlands
Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD, Groningen, the Netherlands
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University Medical Center Groningen · University of Groningen
Affiliation as printed
Department of Pulmonary Diseases University of Groningen, University Medical Center Groningen Groningen the Netherlands
University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD Groningen the Netherlands
Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD, Groningen, the Netherlands
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Alen Faiz corresponding
University of Technology Sydney · The University of Sydney · University Medical Center Groningen · University of Groningen · Woolcock Institute of Medical Research
Affiliation as printed
Department of Pulmonary Diseases University of Groningen, University Medical Center Groningen Groningen the Netherlands
The University of Sydney, Respiratory Cellular and Molecular Biology (RCMB), Woolcock Institute of Medical Research Sydney New South Wales Australia
University of Technology Sydney, Respiratory Bioinformatics and Molecular Biology (RBMB), School of Life Sciences Sydney New South Wales Australia
Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
The University of Sydney, Respiratory Cellular and Molecular Biology (RCMB), Woolcock Institute of Medical Research, Sydney, New South Wales, Australia
University of Technology Sydney, Respiratory Bioinformatics and Molecular Biology (RBMB), School of Life Sciences, Sydney, New South Wales, Australia
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