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COPD and non-diseased nasopharyngeal and bronchial organoids characterization by single cell RNA-seq

ABSTRACT: Clinical COPD, characterised by intermittent and infective exacerbations, lacks cellular model systems for the study of host-pathogen relationships. We establish nasopharyngeal and bronchial organoids from COPD patients and healthy individuals. In contrast to healthy organoids, COPD organoids demonstrate the hallmark goblet cell hyperplasia phenotype with reduced ciliary beat frequency, leading to impaired mucociliary clearance. By single-cell transcriptome analysis, smooth trajectory of cellular differentiation is disrupted in COPD organoids when compared to non-diseased, and functional pathways involved in the development and progression of COPD including mitochondrial dysfunction and sirtuin signalling are activated in the COPD model.

ORGANISM(S): Homo sapiens

PROVIDER: GSE186017 | GEO | 2022/11/10

REPOSITORIES: GEO

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Project description:Study Smoking and COPD are associated with decreased mucociliary clearance and healthy smokers have shorter cilia in the large airway than nonsmokers. Intraflagellar transport (IFT) is the process by which cilia are produced and maintained. We assessed expression of IFT-related genes in smokers and nonsmokers and evaluated cilia length in the large and small airway of nonsmokers, healthy smokers, and smokers with COPD. Methods Airway epithelium was obtained via bronchoscopic brushing. Affymetrix microarrays were used to evaluate IFT gene expression in 2 independent data sets from large and small airway. Cilia length was assessed by measuring 100 cilia (10 cilia on each of 10 cells) per subject. Results All 40 IFT genes were expressed in the human large and small airway epithelium. In the large airway, 10 IFT genes were down-regulated and 1 up-regulated in smokers. In the small airway, 11 genes were down-regulated and 3 up-regulated in smokers. A set of 8 IFT genes was down-regulated in both data sets. In the large and small airway epithelium, cilia were significantly shorter in healthy smokers than nonsmokers, and significantly shorter in COPD smokers than in both healthy smokers and nonsmokers. Answer to the Question These results support the concept that loss of cilia length contributes to defective mucociliary clearance in COPD, and that smoking-induced changes in expression of IFT genes may be one mechanism of abnormally short cilia in smokers. Strategies to normalize cilia length may be an important avenue for novel COPD therapies. Gene expression was assessed for 40 intraflagellar transport related genes in the LAE of nonsmokers (n=21) and healthy smokers (n=31) and the SAE of an independent group of nonsmokers (n=28) and healthy smokers (n=69). Cilia length was assessed in a total of 228 airway epithelium samples, including 120 LAE samples and 108 SAE samples; a subset of the 228 samples is represented among the 149 samples in this Series.

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COPD and non-diseased nasopharyngeal and bronchial organoids characterization by single cell RNA-seq

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