Tobacco smoking induces changes in true DNA methylation, hydroxymethylation and gene expression in bronchoalveolar lavage cells
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ABSTRACT:
PROVIDER: PRJNA549863 | ENA |
REPOSITORIES: ENA
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Project description:Background While smoking is known to associate with development of multiple diseases, the underlying mechanisms are still poorly understood. Tobacco smoking can modify the chemical integrity of DNA leading to changes in transcriptional activity, partly through an altered epigenetic state. We aimed to investigate the impact of smoking on lung cells collected from bronchoalveolar lavage (BAL). Methods We profiled changes in DNA methylation (5mC) and its oxidized form hydroxymethylation (5hmC) using conventional bisulfite (BS) treatment and oxidative bisulfite treatment with Illumina Infinium MethylationEPIC BeadChip, and examined gene expression by RNA-seq in healthy smokers. Findings We identified 1,667 BS methyl (5mC+5hmC), 1,756 5mC and 67 5hmC differentially methylated positions (DMPs) between smokers and nonsmokers (FDR <0.05, absolute Δβ >0.15). Both 5mC DMPs and to a lesser extent BS methyl (5mC+5hmC) were predominantly hypomethylated. In contrast, almost all 5hmC DMPs were hypermethylated, supporting the hypothesis that smoking-associated oxidative stress can lead to DNA demethylation, via the established sequential oxidation of which 5hmC is the first step. While we confirmed differential methylation of previously reported smoking-associated BS methyl CpGs using former generations of BeadChips in alveolar macrophages, the large majority of identified DMPs, BS methyl (1,639/1,667), 5mC (1,738/1,756), and 5hmC (67/67), have not been previously reported. Most of these novel smoking-associating sites are specific to the EPIC BeadChip and, interestingly, many of them are associated to FANTOM5 enhancers. Transcriptional changes affecting 633 transcripts were consistent with DNA methylation profiles and converged to alteration of genes involved in migration, signaling and inflammatory response of immune cells. Interpretation Collectively, these findings suggest that tobacco smoke exposure epigenetically modifies BAL cells, possibly involving a continuous active demethylation and subsequent increased activity of inflammatory processes in the lungs. -
2019-06-21 | GSE133062 | GEO
Project description:bronchoalveolar lavage fluid Metagenome
| PRJNA449183 | ENA
Project description:Bronchoalveolar lavage, sputum, background Metagenome
| PRJNA1003499 | ENA
Project description:Bronchoalveolar Lavage Fluid Pathogen Microbiology
| PRJEB72318 | ENA
Project description:BackgroundWhile smoking is known to associate with development of multiple diseases, the underlying mechanisms are still poorly understood. Tobacco smoking can modify the chemical integrity of DNA leading to changes in transcriptional activity, partly through an altered epigenetic state. We aimed to investigate the impact of smoking on lung cells collected from bronchoalveolar lavage (BAL).MethodsWe profiled changes in DNA methylation (5mC) and its oxidised form hydroxymethylation (5hmC) using conventional bisulphite (BS) treatment and oxidative bisulphite treatment with Illumina Infinium MethylationEPIC BeadChip, and examined gene expression by RNA-seq in healthy smokers.FindingsWe identified 1667 total 5mC + 5hmC, 1756 5mC and 67 5hmC differentially methylated positions (DMPs) between smokers and non-smokers (FDR-adjusted P <.05, absolute Δβ >0.15). Both 5mC DMPs and to a lesser extent 5mC + 5hmC were predominantly hypomethylated. In contrast, almost all 5hmC DMPs were hypermethylated, supporting the hypothesis that smoking-associated oxidative stress can lead to DNA demethylation, via the established sequential oxidation of which 5hmC is the first step. While we confirmed differential methylation of previously reported smoking-associated 5mC + 5hmC CpGs using former generations of BeadChips in alveolar macrophages, the large majority of identified DMPs, 5mC + 5hmC (1639/1667), 5mC (1738/1756), and 5hmC (67/67), have not been previously reported. Most of these novel smoking-associating sites are specific to the EPIC BeadChip and, interestingly, many of them are associated to FANTOM5 enhancers. Transcriptional changes affecting 633 transcripts were consistent with DNA methylation profiles and converged to alteration of genes involved in migration, signalling and inflammatory response of immune cells.InterpretationCollectively, these findings suggest that tobacco smoke exposure epigenetically modifies BAL cells, possibly involving a continuous active demethylation and subsequent increased activity of inflammatory processes in the lungs. FUND: The study was supported by the Swedish Research Council, the Swedish Heart-Lung Foundation, the Stockholm County Council (ALF), the King Gustav's and Queen Victoria's Freemasons' Foundation, Knut and Alice Wallenberg Foundation, Neuro Sweden, and the Swedish MS foundation.
| S-EPMC6710853 | biostudies-literature
Project description:Background Despite compelling evidence that cigarette smoking impacts the risk of developing Multiple Sclerosis (MS), little is known about smoking-associated changes in the primary exposed cells in the lung of patients. We aimed to examine molecular changes occurring in pulmonary immune cells from MS patients in relation to smoking and in comparison to healthy controls (HC). Methods We profiled genome-wide DNA methylation (5mC) and hydroxymethylation (5hmC) in bronchoalveolar lavage (BAL) cells collected from female MS patients (9 smokers, 8 non-smokers) and healthy volunteers (10 smokers, 12 non-smokers), using Illumina Infinium EPIC arrays on conventional (BS) and oxidative (oxBS) bisulfite DNA. We profiled gene expression using RNA-sequencing in non-smoker MS patients and controls. Findings The most prominent changes were found in relation to smoking, with 1376 BS-differentially methylated positions (DMPs), 131 5mC-DMPs and 4 5hmC-DMP (adjusted P < 0.05) differing between MS smokers and non-smokers. Approximately 30% of the affected genes overlapped with smoking-associated changes in HC, leading to a strong common smoking signature in both MS and HC after gene ontology analysis. Smoking in MS patients resulted in additional discrete changes related to neuronal processes. To further explore MS-specific signature, we performed RNA sequencing in BAL cells from non-smoker MS patients and controls. Overall, methylome and transcriptome analyses in non-smokers suggest that BAL cells from MS patients display very subtle but concordant changes associated to genes connected to reduced transcriptional/translational processes and enhanced cellular adhesion and migration, further corroborating findings from animal studies. Interpretation Our study provides new insights into the impact of smoking on lung inflammation in the immunopathogenesis of MS. -
2020-05-22 | GSE151017 | GEO
Project description:Establish a pipeline for identifying bacterial peptides from human bronchoalveolar lavage fluid samples.
2019-06-24 | PXD008273 | Pride
Project description:Clinical bronchoalveolar lavage (BAL) samples Targeted loci
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Project description:Bronchoalveolar lavage of healthy human adults
| PRJNA637757 | ENA
Project description:AJ mouse is susceptible to lung carcinogenesis from urethane treatment and is a good model for human adenocarcinoma. We completed a study using microarray analysis of bronchoalveolar lavage cells from control or urethane treated mice. A unique macrophage expression signature in the lung tumor microenvironment was able to correctly classify the lavage samples. Experiment Overall Design: RNA from bronchoalveolar lavage cells of age matched untreated AJ mice controls (C) or from urethane treated (T) AJ mice was prepared. Datasets were accurately classified using a unique macrophage gene expression signature derived from the tumor microenvironment.
2008-04-07 | E-GEOD-7258 | biostudies-arrayexpress