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Series GSE151017 Query DataSets for GSE151017
Status Public on May 22, 2020
Title Methylome signature of bronchoalveolar cells from Multiple Sclerosis patients in relation to smoking
Organism Homo sapiens
Experiment type Methylation profiling by array
Summary 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.
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Overall design 39 bronchoalveolar lavage samples (mainly alveolar macrophages) from healthy (H) individuals and multiple sclerosis (MS) patients; smokers (S) and nonsmokers (NS). Includes both BS-treated and oxBS-treated samples for 5mC and 5hmC interrogation.
 
Contributor(s) Ringh M, Kular L
Citation(s)
  • Ringh MV, Hagemann-Jensen M, Needhamsen M, Kullberg S et al. Methylome and transcriptome signature of bronchoalveolar cells from multiple sclerosis patients in relation to smoking. Mult Scler 2021 Jun;27(7):1014-1026. PMID: 32729352
Submission date May 21, 2020
Last update date Aug 21, 2020
Contact name Mikael Ringh
Organization name Karolinska Institutet
Street address Medical Epigenetics, CMM L8:00, Karolinska University Hospital Solna
City Stockholm
State/province Choose state (US & Canada)
ZIP/Postal code 17176
Country Sweden
 
Platforms (1)
GPL23976 Illumina Infinium HumanMethylation850 BeadChip
Samples (78)
GSM4564348 BS_HNS_BAL_641
GSM4564349 BS_HNS_BAL_694
GSM4564350 BS_HS_BAL_698
Relations
BioProject PRJNA634374

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE151017_RAW.tar 1.1 Gb (http)(custom) TAR (of IDAT)
Processed data included within Sample table

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