RNA-seq of human small airawy epithelial cells in patients with COPD and Never-smoker
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE162154 | GEO | 2021/06/10
REPOSITORIES: GEO
Similar Datasets
Project description:Chronic obstructive pulmonary disease (COPD) is a progressive disease that obstructs the airflow from the lungs, and tobacco smoking is the major cause of COPD. Here, we applied single-cell RNA sequencing to analyze COPD pathogenesis in COPD patients, non-COPD smokers and never-smokers and investigated the disease progression at single-cell resolution. By single-cell transcriptome analysis, COPD was characterized by shifts in the stromal, immune system and epithelial cell compositions. While epithelial components in never-smokers were relatively uniform, the smoker groups presented with extensive heterogeneity in epithelial cells, particularly in the alveolar type II (AT2) lineages. We identified a subpopulation of AT2 epithelial cells that emerged in smokers, such as COPD patients, and specifically expressed a series of chemokines and PD-L1. A trajectory analysis revealed that the inflammatory AT2 cell subpopulation followed a unique differentiation path, and a prediction model of cell-to-cell interactions inferred increased intercellular networks of inflammatory AT2 cells with immune and stromal cell populations. Thus, our analysis reveals a unique cellular differentiation pathway and function underlying the biological and clinical characteristics of COPD pathogenesis.
2021-06-29 | GSE173896 | GEO
Project description:Chronic obstructive pulmonary disease (COPD) is one of the most prevalent lung diseases, and involves persistent airflow limitation and incorporates both emphysema and chronic bronchitis. Cigarette smoking has been identified as the main risk factor for disease development and progression. In a basic model of COPD, the disease is initiated when the physiologic response mechanisms to cigarette smoke exposure are overwhelmed; for example, because of long-term exposure effects or other aging-related changes. In this parallel-group case-controlled clinical study we asked to what extent the different transitions in a chronic-exposure-to-disease model are reflected in the proteome and cellular transcriptome of induced sputum samples from the lung. For this, we selected 60 age- and gender-matched individuals for each of four study groups: current healthy smokers, current-smoker COPD patients, former smokers, and never smokers (a total of 240 individuals). Induced sputum was collected, the cell-free supernatant was analyzed by quantitative proteomics (isobaric-tag based), and the cellular mRNA fraction was analyzed by microarray-based expression profiling. The sputum proteome of current smokers (healthy or COPD patients) clearly reflected the common physiological responses to smoke exposure, including alterations in mucin/trefoil proteins (e.g., MUC5AC and TFF1/3up-regulation), peptidase regulators (e.g., TIMP1 up-regulation), and a prominent xenobiotic/oxidative stress response (e.g., NQO1 and ALDH3A1 up-regulation). The latter response also was observed in the sputum transcriptome, which additionally demonstrated an immune-related polarization change (toward a M2 signature). The (long-term) former smoker group showed nearly complete reversal of the observable biological effects. Thirteen differentially abundant proteins between the COPD and healthy smoker groups were identified. These abundant proteins included previously reported COPD-associated proteins (e.g., TIMP1 (up-regulation) and APOA1 (down-regulation)) and novel proteins such as C6orf58 and BPIFB1 (LPLUNC1) (both up-regulated in the COPD group compared with the healthy smokers). In summary, our study demonstrates that sputum proteomics/transcriptomics can capture the complex and reversible physiological response to cigarette smoke exposure, which appears to be only slightly modulated in early-stage COPD patients. The study has been registered on ClinicalTrials.gov with identifier NCT01780298.
2015-08-28 | PXD001977 | Pride
Project description:Cytologically normal airway epithelial samples were collected during bronchoscopy of current and former smokers. Subjects enrolled in this study were either under suspicion of having lung cancer, had dysplasia in their airway, or were a healthy current, former or never smoker. We supplemented existing GEO series (GSE4115 and GSE7895) with the samples in this study to explore PI3K pathway activity in the these cohorts. This study contains: 2 arrays from smokers with COPD (no lung cancer), 1 array from smoker without COPD (no lung cancer); 2 samples from patients with lung cancer, 2 samples from patients without lung cancer; 20 samples from 10 matched individuals with airway dysplasia before and after treatment with myo-inositol, 6 additional samples from individuals with airway dysplasia; 27 samples from mammary epithelial cells used in oncogenic pathway analysis that have either the PI3K pathway activated, the Np63 pathway activated, or are a GFP control.
2010-04-11 | E-GEOD-12815 | biostudies-arrayexpress
Project description:Chronic obstructive pulmonary disease (COPD) is one of the most prevalent lung diseases, and involves persistent airflow limitation and incorporates both emphysema and chronic bronchitis. Cigarette smoking has been identified as the main risk factor for disease development and progression. In a basic model of COPD, the disease is initiated when the physiologic response mechanisms to cigarette smoke exposure are overwhelmed; for example, because of long-term exposure effects or other aging-related changes. In this parallel-group case-controlled clinical study we asked to what extent the different transitions in a chronic-exposure-to-disease model are reflected in the proteome and cellular transcriptome of induced sputum samples from the lung. For this, we selected 60 age- and gender-matched individuals for each of four study groups: current healthy smokers, current-smoker COPD patients, former smokers, and never smokers (a total of 240 individuals). Induced sputum was collected, the cell-free supernatant was analyzed by quantitative proteomics (isobaric-tag based), and the cellular mRNA fraction was analyzed by microarray-based expression profiling. The sputum proteome of current smokers (healthy or COPD patients) clearly reflected the common physiological responses to smoke exposure, including alterations in mucin/trefoil proteins (e.g., MUC5AC and TFF1/3up-regulation), peptidase regulators (e.g., TIMP1 up-regulation), and a prominent xenobiotic/oxidative stress response (e.g., NQO1 and ALDH3A1 up-regulation). The latter response also was observed in the sputum transcriptome, which additionally demonstrated an immune-related polarization change (toward a M2 signature). The (long-term) former smoker group showed nearly complete reversal of the observable biological effects. Thirteen differentially abundant proteins between the COPD and healthy smoker groups were identified. These abundant proteins included previously reported COPD-associated proteins (e.g., TIMP1 (up-regulation) and APOA1 (down-regulation)) and novel proteins such as C6orf58 and BPIFB1 (LPLUNC1) (both up-regulated in the COPD group compared with the healthy smokers). In summary, our study demonstrates that sputum proteomics/transcriptomics can capture the complex and reversible physiological response to cigarette smoke exposure, which appears to be only slightly modulated in early-stage COPD patients. The study has been registered on ClinicalTrials.gov with identifier NCT01780298.
2016-10-21 | MSV000080275 | MassIVE
Project description:Chronic obstructive pulmonary disease (COPD) is one of the most prevalent lung diseases, and involves persistent airflow limitation and incorporates both emphysema and chronic bronchitis. Cigarette smoking has been identified as the main risk factor for disease development and progression. In a basic model of COPD, the disease is initiated when the physiologic response mechanisms to cigarette smoke exposure are overwhelmed; for example, because of long-term exposure effects or other aging-related changes. In this parallel-group case-controlled clinical study we asked to what extent the different transitions in a chronic-exposure-to-disease model are reflected in the proteome and cellular transcriptome of induced sputum samples from the lung. For this, we selected 60 age- and gender-matched individuals for each of four study groups: current healthy smokers, current-smoker COPD patients, former smokers, and never smokers (a total of 240 individuals). Induced sputum was collected, the cell-free supernatant was analyzed by quantitative proteomics (isobaric-tag based), and the cellular mRNA fraction was analyzed by microarray-based expression profiling. The sputum proteome of current smokers (healthy or COPD patients) clearly reflected the common physiological responses to smoke exposure, including alterations in mucin/trefoil proteins (e.g., MUC5AC and TFF1/3up-regulation), peptidase regulators (e.g., TIMP1 up-regulation), and a prominent xenobiotic/oxidative stress response (e.g., NQO1 and ALDH3A1 up-regulation). The latter response also was observed in the sputum transcriptome, which additionally demonstrated an immune-related polarization change (toward a M2 signature). The (long-term) former smoker group showed nearly complete reversal of the observable biological effects. Thirteen differentially abundant proteins between the COPD and healthy smoker groups were identified. These abundant proteins included previously reported COPD-associated proteins (e.g., TIMP1 (up-regulation) and APOA1 (down-regulation)) and novel proteins such as C6orf58 and BPIFB1 (LPLUNC1) (both up-regulated in the COPD group compared with the healthy smokers). In summary, our study demonstrates that sputum proteomics/transcriptomics can capture the complex and reversible physiological response to cigarette smoke exposure, which appears to be only slightly modulated in early-stage COPD patients. The study has been registered on ClinicalTrials.gov with identifier NCT01780298.
2015-08-28 | E-MTAB-3604 | biostudies-arrayexpress
Project description:Rationale: COPD is characterized by an abnormal regulatory T cell (Treg) response and increases in Th1 and Th17 cell responses. It is unclear if dysregulation of miRNAs within Treg alters the adaptive immunophenotype in COPD. Objectives: To compare the miRNA profile of COPD Treg cells with that of healthy controls and to explore the function of differentially expressed miRNAs. Methods: Treg cells (CD4+CD25+CD49-CD127-) and T effector (CD4+CD25-) cells were obtained from the peripheral blood of 4 nonsmokers, 4 healthy current smokers, and 4 COPD current smokers for analysis of miRNA expression, matching them for age and sex. We assessed expression initially by microarray analysis on the Illumina miRNA platform then conducted real time RT-PCR validation of the microarray results. 24 samples were analyzed. 8 from each patient group of healthy Normal, Healthy Smoker, and COPD Smoker.
2014-04-19 | E-GEOD-56923 | biostudies-arrayexpress
Project description:mRNA expression was profiled from pooled bronchial airway epithelial cell brushings (n=3 patients/pool) obtained during bronchoscopy from healthy never (NS) and current smokers (S) and smokers with (C) and without (NC) lung cancer 4 samples were sequened, each representing a pool of 3 patients. The phenotypes of the 4 samples were as follows: healthy non-smoker, healthy smoker, smoker without lung cancer and smoker with lung cancer.
2011-06-01 | E-GEOD-29006 | biostudies-arrayexpress
Project description:Rationale: Genome-wide association studies (GWAS) and candidate gene studies have identified a number of loci linked to susceptibility of chronic obstructive pulmonary disease (COPD), a smoking-related disorder that originates in the airway epithelium. Objectives: Since airway basal cell (BC) stem/progenitor cells exhibit the earliest abnormalities associated with smoking (hyperplasia, squamous metaplasia), we hypothesized that smoker BC have a dysregulated transcriptome linked, in part, to known GWAS/candidate gene loci. Methods: Massive parallel RNA sequencing was used to compare the transcriptome of BC purified from the airway epithelium of healthy nonsmokers (n=10) and smokers (n=7). The chromosomal location of the differentially expressed genes was compared to loci identified by GWAS and candidate gene studies to confer risk for COPD. Measurements and Main Results: Smoker BC have 676 known genes differentially expressed compared to nonsmoker BC, dominated by smoking up-regulation. Strikingly, 166 (25%) of these genes are located on chromosome 19, with 13 localized to 19q13.2 (p<10-4 compared to chance), including TGFB1, LTBP4, EGLN2 and NFKBIB, genes associated with risk for COPD. Conclusions: These observations provide the first direct link of known genetic risks for smoking-related lung disease with the specific population of lung cells that undergoes the earliest changes associated with smoking. The human airway basal cell transcriptome of 7 smokers versus 10 nonsmokers was compared using massive parallel RNA sequencing (Illumina HiSeq 2000).
2014-05-08 | E-GEOD-47718 | biostudies-arrayexpress
Project description:Continuous stress caused by smoking induces changes in the cell population of small airway epithelium, with basal cell hyperplasia and goblet cell metaplasia at the expense of ciliated cells, and there is now compiling evidence that basal cells play a key role in the early pathogenesis of Chronic Obtructive Pulmonary Disease (COPD). We hypothesized that COPD airway basal cells undergo transcriptomic changes during differentiation that are different from those observed in normal cells and can explain the formation of an abnormal epithelium. We performed microarray analysis of basal cells obtained from healthy non-smoker and COPD subjects and also mucociliary-differentiated cell cultures from the same basal cells. We compared the transcriptome of normal and COPD basal cells, mucociliary-differentiated normal and COPD cell cultures and also of basal cells with corresponding mucociliary-differentiated cultures for both normal and COPD.
2020-10-31 | GSE137557 | GEO
Project description:Approximately 15% of lung cancer cases are not associated with smoking and show molecular and clinical characteristics distinct from those in smokers. Epidermal growth factor receptor (EGFR) gene mutations, which are correlated with sensitivity to EGFR-tyrosine kinase inhibitors (EGFR-TKIs), are more frequent in never-smoker lung cancers. In this study, microRNA (miRNA) expression profiling of 28 never-smoker lung cancer cases identified aberrantly expressed miRNAs, which were much fewer than in lung cancers of smokers and included miRNAs previously identified (e.g., upregulated miR-21) and unidentified (e.g., downregulated miR-138) in those smoker cases. The changes in expression of some of these miRNAs were more remarkable in cases with EGFR mutations than in those without: the most upregulated miRNA, miR-21, was more abundant in cancers with EGFR mutation. A significant correlation between phosphorylated-EGFR (p-EGFR) and miR-21 levels in lung carcinoma cell lines and the suppression of miR-21 by an EGFR-TKI, AG1478, suggested that the EGFR signaling pathway positively regulated miR-21 expression. In a never-smoker-derived lung adenocarcinoma cell line H3255 with mutant EGFR and high levels of p-EGFR and miR-21, antisense inhibition of miR-21 enhanced AG1478-induced apoptosis. In a never-smoker-derived adenocarcinoma cell line H441 with wild-type EGFR, the antisense miR-21 not only showed the additive effect with AG1478 but also induced apoptosis by itself. These results suggest that aberrantly increased expression of miR-21, which is further enhanced by the activated EGFR signaling pathway, plays a critical role in lung carcinogenesis in never-smokers and is a potential therapeutic target in both EGFR mutant and wild-type cases. Twenty-eight pairs of lung cancer tissues and corresponding noncancerous lung tissues were obtained from never-smokers who had undergone surgical resection from 2000 to 2004 at the University of Maryland Medical Center (n=15), Mayo Clinic (n=7) in United States and Hamamatsu University School of Medicine (n=6) in Japan.
2010-05-15 | E-GEOD-14936 | biostudies-arrayexpress