6aa2f6b8-06f0-407d-ac4f-c7d2a022abdf - samples
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PROVIDER: EGAD00001009406 | EGA |
REPOSITORIES: EGA
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Project description:Primary lung fibroblast were isolated from well-matched control donors (no COPD, n=3) and patients with COPD (GOLD stage I-IV, n=8). Total RNA of cultured human lung fibroblast were isolated at passage 3 and rRNA was depleted. 75 bp single-end reads were generated from RNA libraries on Illumina NextSeq 500.
| EGAD00001009405 | EGA
Project description:Chronic obstructive pulmonary disease (COPD) collectively refers to chronic and progressive lung diseases causing not fully reversible limitations in airflow. COPD patients are at high risk for severe respiratory symptoms upon influenza virus infection. Airway epithelial cells provide the first-line antiviral defense, but whether their susceptibility and response to influenza virus infection changes in COPD has not been elucidated. Therefore, this study aimed to i) compare the susceptibility of COPD- and control-derived airway epithelium to influenza virus, and ii) assess protein changes during influenza virus infection by quantitative proteomics. Fluorescent stainings confirmed expression of human- and avian-type influenza virus receptors in primary human bronchial epithelial cells (phBECs) from COPD patients (n=4) and controls (n=3) differentiated at the air-liquid interface. Subjects were closely matched in age, sex, and smoking history and, for COPD-derived phBECs, included stage II (n=2), stage III (n=1) and stage IV (n=1). Proteomics of fully differentiated phBECs pre- and post-influenza A virus infection with A/Puerto Rico/8/34 (PR8) revealed no significant differences between GOLD stage II/ III COPD (n=3) and control phBECs in terms of flu receptor expression, cell type composition, virus replication, or protein profile pre- and post-infection. In contrast, COPD GOLD stage IV phBECs (n=1) showed a distinct pattern of flu receptor expression and a typical COPD phenotype as assessed by a literature-derived panel of 20 proteins and quantification of cell type composition. Independent of health state, proteomics showed a robust antiviral response to influenza virus infection, as well as upregulation of several novel influenza virus-regulated proteins.
2022-12-29 | PXD031461 | Pride
Project description:We have constructed a transcriptomic map of airways using lung tissues from three COPD (GOLD grade I) who underwent surgical resection for lung cancer. We performed 5' single-cell RNA sequencing (scRNA-seq) on three COPD and three control matched lung tissue, as well as the organoid samples.
2024-06-28 | GSE270667 | GEO
Project description:Chronic obstructive pulmonary disease (COPD) is an independent risk factor for lung cancer, suggesting that COPD stroma favors cancer initiation. Therefore, we used proteomics and polysome-profiling to identify gene expression programs that distinguish stroma of patients harboring lung cancer from those that do not, with varied COPD severities. This profiling unveiled distinct COPD-dependent cancer-associated gene expression programs predominantly manifesting as alterations in mRNA translation. Mechanistically, such programs are downstream of the mammalian target of rapamycin pathway in mild COPD and pathological extracellular matrix in more severe COPD; and both programs parallel activation of distinct pro-cancer fibroblast-derived secretomes. Therefore, depending upon COPD severity, the lung stroma can exist in two states favoring cancer initiation, which likely result in distinct disease entities.
2021-11-03 | PXD007743 | Pride
Project description:70 miRNAs and 2667 mRNAs were differentially expressed between lung tissue from subjects with COPD and smokers without COPD. miRNA and mRNA expression profiles enriched for biological pathways that may be relevant to the pathogenesis of COPD including the transforming growth factor b, Wnt and focal adhesion pathways. miR-223 and miR-1274a were the most affected miRNAs in subjects with COPD compared with smokers without obstruction. miR-15b was increased in COPD samples compared with smokers without obstruction and localised to both areas of emphysema and fibrosis. miR-15b was differentially expressed within GOLD classes of COPD. Expression of SMAD7, which was validated as a target for miR-15b, was decreased in bronchial epithelial cells in COPD. Lung tissue from smokers with no evidence of obstructive lung disease and smokers with COPD was examined for miRNA and mRNA expression followed by validation. We then examined both miRNA and mRNA expression to enrich for relevant biological pathways
2012-06-26 | E-GEOD-38974 | biostudies-arrayexpress
Project description:COPD is a common and disabling lung disease for which very few therapeutic options are currently available. We reasoned that global gene expression profiling of COPD lungs could reveal previously unidentified disease pathways for potential therapeutic interventions. Forty-eight human lung samples were obtained from lungs or lobes resected for small peripheral lung lesions (5 non-smokers, 21 GOLD 0, 9 GOLD 1, 10 GOLD 2 and 3 GOLD 3 patients). mRNA from the specimens was profiled using Agilent’s Functional ID v2.0 array which contains 23,720 sequences. Quantitative morphometric analysis of the specimens revealed that the samples contained a variable proportion of airways, blood vessels and parenchyma. Incorporating these data into a model relating gene expression to % predicted forced expiratory flow between 25 and 75% of forced expiratory volume (FEF 25-75 % P) revealed a signature gene set of 203 transcripts. Genes involved in extracellular matrix synthesis/degradation, oxidative stress and cell proliferation were among the up-regulated genes whereas genes which participate in nicotine metabolism, elastic fiber homeostasis and anti-inflammatory response were down-regulated. Immunohistochemistry confirmed expression of urokinase (PLAU), urokinanse receptor (PLAUR) and thrombospondin (THBS1) by alveolar macrophages and small airway epithelial cells. Genes in this pathway have been shown to be involved in transforming growth factor beta-1 (TGF?1) and matrix metalloproteinase (MMP) activation and are subject to inhibition by serpin E2. Interestingly, both TGF?1 and serpin E2 have been identified as candidate genes in COPD genetic linkage and association studies. The results thus provide a possible link between these two powerful approaches to identify potential therapeutic targets. (255 words) Forty-eight human lung samples were obtained from lungs or lobes resected for small peripheral lung lesions (5 non-smokers, 21 GOLD 0, 9 GOLD 1, 10 GOLD 2 and 3 GOLD 3 patients). mRNA from the specimens was profiled using Agilent’s Functional ID v2.0 array which contains 23,720 sequences. Quantitative morphometric analysis of the specimens revealed that the samples contained a variable proportion of airways, blood vessels and parenchyma. Incorporating these data into a model relating gene expression to % predicted forced expiratory flow between 25 and 75% of forced expiratory volume (FEF 25-75 % P) revealed a signature gene set of 203 transcripts.
2007-11-09 | E-GEOD-8500 | biostudies-arrayexpress
Project description:Adult lung resident stem/progenitor cells, including P63+ progenitor cells, have demonstrated the capacity for regeneration of lung epithelium in precinical models. Here we report a clinical trial of intra-pulmonary P63+ progenitor cell transplantation which included 28 participants with chronic obstructive pulmonary disease (COPD) (stage II~IV). For control group, standard of care (SOC) for COPD treatment was given. For intervention group, in addition to SOC, autologous P63+ progenitor cells were isolated from the airway basal layer via bronchoscopic brushing, cultured for 3~5 weeks, and then transplanted into the lungs via bronchoscopy with 0.7-5.2x10^6 cells per kilogram bodyweight. Eventually 20 patients were evaluated (intervention group n=17; control group n=3). No grade 3~5 adverse events (AE) or serious adverse events occurred in any group. Bronchoscopy-associated AEs were recorded only in intervention groups, while the other AEs were recorded in both groups without showing significant difference. Participants in intervention group displayed significant improvement in diffusing capacity of the lung for carbon monoxide (DLCO) (change from baseline, 24 weeks: +18.2%), showing significant difference comparing to control group (change from baseline, 24 weeks: -17.4%)(p-value=0.008). Furthermore, more participants in intervention group showed > 30 m increase in walking distance within 6 minutes, demonstrating significant difference comparing to control group (p-value=0.036). Transcriptomic analysis of cells isolated from responding and non-responding individuals in the intervention group showed that higher expression of P63 and Nkx homeobox-1 was associated with better efficacy. In conclusion, transplantation of cultured P63+ lung progenitor cells was safe and represented a potential treatment strategy for COPD.
2024-01-20 | GSE236438 | GEO
Project description:70 miRNAs and 2667 mRNAs were differentially expressed between lung tissue from subjects with COPD and smokers without COPD. miRNA and mRNA expression profiles enriched for biological pathways that may be relevant to the pathogenesis of COPD including the transforming growth factor b, Wnt and focal adhesion pathways. miR-223 and miR-1274a were the most affected miRNAs in subjects with COPD compared with smokers without obstruction. miR-15b was increased in COPD samples compared with smokers without obstruction and localised to both areas of emphysema and fibrosis. miR-15b was differentially expressed within GOLD classes of COPD. Expression of SMAD7, which was validated as a target for miR-15b, was decreased in bronchial epithelial cells in COPD.
2012-06-27 | GSE38974 | GEO
Project description:Epigenetics changes have been shown to be affected by cigarette smoking. It is possible that cigarette smoke (CS)-mediated DNA methylation would affect several cellular and pathophysiological processes, acute exacerbations, and comorbidity in lungs of patients with chronic obstructive pulmonary disease (COPD). We sought to determine whether genome-wide lung DNA methylation profiles of smokers and patients with COPD were significantly different from non-smokers. We isolated DNA from lung tissues of patients including 8 lifelong non-smokers, 8 current smokers, and 8 patients with COPD, and subsequently analyzed the samples using the Illumina’s Infinium HumanMethylation450 BeadChip.
2017-06-12 | GSE92511 | GEO
Project description:Airway basal cells are crucial for regeneration of the human lung airway epithelium, and are thought to be important contributors to chronic obstructive pulmonary disease (COPD). However, to reveal how basal cells contribute to disease, the basal cells need to be further characterized. We aimed to study primary human basal cells from healthy donors and COPD patients in order to identify key differences that could further our understanding of the disease mechanisms. In this study, we optimized a sorting protocol for primary human basal cells dependent on cell size and NGFR expression. The basal cell population was found to be heterogeneous in contrast to cultured basal cells. In addition, significant differences such as KRT14 expression was found exclusively in cultured cells. Also, colony-forming capacity was significantly increased in cultured cells showing a clonal enrichment in vitro. Next, by single cell RNA sequencing on primary basal cells from healthy donors and COPD patients, the gene expression changes revealed a continuum ranging from healthy basal cell signatures to diseased basal cells phenotypes. We identified several upregulated genes that may be indicative of COPD, such as stress response related genes GADD45B and AHSA1, along with genes involved in the response to hypoxia such as CITED2 and SOD1. Taken together, the presence of both healthy and diseased basal cells in stage IV COPD demonstrates the potential for regeneration through the discovery of novel therapeutic targets. In addition, we show the importance of studying primary basal cells when investigating disease mechanisms in the human lung.
2021-03-01 | GSE158942 | GEO