Characterizing smoking-induced transcriptional heterogeneity in the human bronchial epithelium at single-cell resolution
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ABSTRACT:
PROVIDER: PRJNA543474 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9079180_1.fastq.gz | Fastqsanger.gz | |||
| SRR9079180_2.fastq.gz | Fastqsanger.gz | |||
| SRR9079181_1.fastq.gz | Fastqsanger.gz | |||
| SRR9079181_2.fastq.gz | Fastqsanger.gz | |||
| SRR9079182_1.fastq.gz | Fastqsanger.gz |
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Project description:The human bronchial epithelium is composed of multiple, distinct cell types that cooperate to defend against environmental insults. While studies have shown that smoking alters bronchial epithelial function and morphology, its precise effects on specific cell types and overall tissue composition are unclear. We used single-cell RNA sequencing to profile bronchial epithelial cells from six never- and six current smokers. Unsupervised analyses led to the characterization of a set of toxin metabolism genes that localized to smoker ciliated cells, tissue remodeling associated with a loss of club cells and extensive goblet cell hyperplasia, and a novel peri-goblet epithelial subpopulation in smokers that expressed a marker of bronchial premalignant lesions. Our data demonstrates that smoke exposure drives a complex landscape of cellular alterations that may prime the human bronchial epithelium for disease.
2019-09-27 | GSE131391 | GEO
Project description:Cigarette smoking is the main risk factor for the development of squamous cell lung carcinoma (SCC). However, the smoking-related molecular changes in SCC have not been studied. We wanted to identify genes in both histologically normal bronchial epithelium and SCC samples that are differentially expressed between current and ex-smokers. In addition, to analyze the levels of the smoking-related genes identified in normal bronchial epithelium with the levels in SCC. Gene expression profiles were generated using Agilent whole human genome microarrays in 28 laser microdissected normal bronchus epithelial samples and in 35 laser microdissected SCC samples of current and ex-smokers. Levels of 246 genes, mainly related to oxidative stress response, were significantly different between normal bronchial epithelium of current and ex-smokers. No significant differences were associated with the smoking status in SCC samples. Analysis of the 246 smoking specific genes in SSC from current and ex-smokers also revealed no differences. As a next step, we compared the levels of the smoking-specific gene signature between normal bronchial epithelium from ex- and current smokers to all 34 SCC samples. Twenty-two percent of the upregulated genes are further upregulated in SCC as compared to current smokers. Expression of the downregulated genes was even further downregulated for 79% of the genes in SCC as compared to bronchus epithelium of current smokers. The downregulated genes included several tumour suppressor genes. This study shows that genes upregulated in normal bronchial epithelium of current smokers are expressed at similar levels in SCC samples, while levels of downregulated genes were significantly further reduced in SCC. This indicates that these downregulated genes play a role in SCC oncogenesis.
2008-10-01 | GSE12428 | GEO
Project description:The human bronchial epithelium is composed of multiple distinct cell types that cooperate to defend against environmental insults. While studies have shown that smoking alters bronchial epithelial function and morphology, its precise effects on specific cell types and overall tissue composition are unclear. We used single-cell RNA sequencing to profile bronchial epithelial cells from six never and six current smokers. Unsupervised analyses led to the characterization of a set of toxin metabolism genes that localized to smoker ciliated cells, tissue remodeling associated with a loss of club cells and extensive goblet cell hyperplasia, and a previously unidentified peri-goblet epithelial subpopulation in smokers who expressed a marker of bronchial premalignant lesions. Our data demonstrate that smoke exposure drives a complex landscape of cellular alterations that may prime the human bronchial epithelium for disease.
| S-EPMC6905872 | biostudies-literature
Project description:Characterizing hookah smoking-induced transcriptional regulations in the human bronchial epithelial cell
| PRJNA681798 | ENA
Project description:19 bronchial epithelial SAGE libraries were constructed and analyzed in this study. Discussed in the study: IDENTIFICATION OF NOVEL LUNG GENES IN BRONCHIAL EPITHELIUM BY SERIAL ANALYSIS OF GENE EXPRESSION Kim M. Lonergan1, Raj Chari1, Ronald J. deLeeuw1, Ashleen Shadeo1, Bryan Chi1, Ming-Sound Tsao2, Steven Jones3, Marco Marra3, Victor Ling1, Raymond Ng1,4, Calum MacAulay5, Stephen Lam5 and Wan L. Lam1 From the 1Department of Cancer Genetics & Developmental Biology, 5Department of Cancer Imaging, 3Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Research Centre, Vancouver, BC, Canada, 2Ontario Cancer Institute / Princess Margaret Hospital, Toronto, ON, Canada, 4the Department of Computer Science, University of British Columbia, Vancouver, BC, Canada A description of the transcriptome of human bronchial epithelium should provide a basis for studying lung diseases including cancer. We demonstrate here that minute epithelial specimens obtained by bronchial brushings afford reliable profiling by serial analysis of gene expression (SAGE) leading to lung gene discovery. We have deduced global gene expression profiles of bronchial epithelium and lung parenchyma, based upon a vast data set of nearly two million sequence tags from 21 SAGE libraries generated from individuals with a history of smoking. Cluster and linear regression analysis demonstrate the repeatability and reproducibility of bronchial SAGE libraries, and suggest that the transcriptome of the bronchial epithelium is distinct from that of lung parenchyma and other tissue types. This distinction is highlighted by the abundant expression of signature genes that reflect tissue-specific and region-specific functions. Through our analysis we have identified novel bronchial-enriched genes and a novel transcript variant for surfactant, pulmonary-associated protein B in lung parenchyma. Conspicuously, gene expression associated with ciliogenesis is evident in bronchial epithelium. Additionally, it is noted that a large number of unmapped tags awaits further investigation. This study represents a comprehensive delineation of the bronchial and parenchyma transcriptomes, identifying more than 20,000 known and hypothetical genes expressed in the human lung, constituting one of the largest human SAGE studies reported to date. Keywords: bronchial epithelium 19 bronchial epithelial SAGE libraries were constructed and analyzed in this study.
2006-07-14 | E-GEOD-3707 | biostudies-arrayexpress
Project description:19 bronchial epithelial SAGE libraries were constructed and analyzed in this study. Discussed in the study: IDENTIFICATION OF NOVEL LUNG GENES IN BRONCHIAL EPITHELIUM BY SERIAL ANALYSIS OF GENE EXPRESSION Kim M. Lonergan1, Raj Chari1, Ronald J. deLeeuw1, Ashleen Shadeo1, Bryan Chi1, Ming-Sound Tsao2, Steven Jones3, Marco Marra3, Victor Ling1, Raymond Ng1,4, Calum MacAulay5, Stephen Lam5 and Wan L. Lam1 From the 1Department of Cancer Genetics & Developmental Biology, 5Department of Cancer Imaging, 3Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Research Centre, Vancouver, BC, Canada, 2Ontario Cancer Institute / Princess Margaret Hospital, Toronto, ON, Canada, 4the Department of Computer Science, University of British Columbia, Vancouver, BC, Canada A description of the transcriptome of human bronchial epithelium should provide a basis for studying lung diseases including cancer. We demonstrate here that minute epithelial specimens obtained by bronchial brushings afford reliable profiling by serial analysis of gene expression (SAGE) leading to lung gene discovery. We have deduced global gene expression profiles of bronchial epithelium and lung parenchyma, based upon a vast data set of nearly two million sequence tags from 21 SAGE libraries generated from individuals with a history of smoking. Cluster and linear regression analysis demonstrate the repeatability and reproducibility of bronchial SAGE libraries, and suggest that the transcriptome of the bronchial epithelium is distinct from that of lung parenchyma and other tissue types. This distinction is highlighted by the abundant expression of signature genes that reflect tissue-specific and region-specific functions. Through our analysis we have identified novel bronchial-enriched genes and a novel transcript variant for surfactant, pulmonary-associated protein B in lung parenchyma. Conspicuously, gene expression associated with ciliogenesis is evident in bronchial epithelium. Additionally, it is noted that a large number of unmapped tags awaits further investigation. This study represents a comprehensive delineation of the bronchial and parenchyma transcriptomes, identifying more than 20,000 known and hypothetical genes expressed in the human lung, constituting one of the largest human SAGE studies reported to date. Keywords: bronchial epithelium
2006-07-14 | GSE3707 | GEO
Project description:A description of the transcriptome of human bronchial epithelium should provide a basis for studying lung diseases including cancer. We demonstrate here that minute epithelial specimens obtained by bronchial brushings afford reliable profiling by serial analysis of gene expression (SAGE) leading to lung gene discovery. We have deduced global gene expression profiles of bronchial epithelium and lung parenchyma, based upon a vast data set of nearly two million sequence tags from 21 SAGE libraries generated from individuals with a history of smoking. Cluster and linear regression analysis demonstrate the repeatability and reproducibility of bronchial SAGE libraries, and suggest that the transcriptome of the bronchial epithelium is distinct from that of lung parenchyma and other tissue types. This distinction is highlighted by the abundant expression of signature genes that reflect tissue-specific and region-specific functions. Through our analysis we have identified novel bronchial-enriched genes and a novel transcript variant for surfactant, pulmonary-associated protein B in lung parenchyma. Conspicuously, gene expression associated with ciliogenesis is evident in bronchial epithelium. Additionally, it is noted that a large number of unmapped tags awaits further investigation. This study represents a comprehensive delineation of the bronchial and parenchyma transcriptomes, identifying more than 20,000 known and hypothetical genes expressed in the human lung, constituting one of the largest human SAGE studies reported to date. Keywords: SuperSeries This reference Series links data in the following related Series: GSE3707 Expression profiling of bronchial epithelium GSE3708 Expression profiling of normal lung parenchyma
2006-11-20 | E-GEOD-3754 | biostudies-arrayexpress
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.
2022-10-25 | GSE210659 | GEO
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.
2022-10-25 | GSE210694 | GEO
Project description:A description of the transcriptome of human bronchial epithelium should provide a basis for studying lung diseases including cancer. We demonstrate here that minute epithelial specimens obtained by bronchial brushings afford reliable profiling by serial analysis of gene expression (SAGE) leading to lung gene discovery. We have deduced global gene expression profiles of bronchial epithelium and lung parenchyma, based upon a vast data set of nearly two million sequence tags from 21 SAGE libraries generated from individuals with a history of smoking. Cluster and linear regression analysis demonstrate the repeatability and reproducibility of bronchial SAGE libraries, and suggest that the transcriptome of the bronchial epithelium is distinct from that of lung parenchyma and other tissue types. This distinction is highlighted by the abundant expression of signature genes that reflect tissue-specific and region-specific functions. Through our analysis we have identified novel bronchial-enriched genes and a novel transcript variant for surfactant, pulmonary-associated protein B in lung parenchyma. Conspicuously, gene expression associated with ciliogenesis is evident in bronchial epithelium. Additionally, it is noted that a large number of unmapped tags awaits further investigation. This study represents a comprehensive delineation of the bronchial and parenchyma transcriptomes, identifying more than 20,000 known and hypothetical genes expressed in the human lung, constituting one of the largest human SAGE studies reported to date. This SuperSeries is composed of the SubSeries listed below.
2006-11-21 | GSE3754 | GEO