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

ABSTRACT: Smoking modulates different secretory subpopulations expressing SARS-CoV-2 entry genes in the nasal and bronchial airways (DECAMP nasal brushings)

PROVIDER: PRJNA866712 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR20907500_1.fastq.gz	Fastqsanger.gz
	SRR20907500_2.fastq.gz	Fastqsanger.gz
	SRR20907600_1.fastq.gz	Fastqsanger.gz
	SRR20907600_2.fastq.gz	Fastqsanger.gz
	SRR20907700_1.fastq.gz	Fastqsanger.gz

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

Project 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. AQ1 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, smokinginduced 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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Project description:Nasal epithelial brushings were prospectively collected from current and former smokers with pulmonary lesions suspicious for lung cancer in the AEGIS-1 (n=375) and AEGIS-2 (n=130) clinical trials and gene expression profiled using microarrays.

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

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Project description:Smoking modulates different secretory subpopulations expressing SARS-CoV-2 entry genes in the nasal and bronchial airways (DECAMP bronchial brushings)

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