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Genome-wide DNA methylation profiling identifies epigenetic changes in CD4+ and CD14+ cells of multiple sclerosis patients [CD14]

ABSTRACT: Genome-wide DNA methylation profiling identifies epigenetic changes in CD4+ and CD14+ cells of multiple sclerosis patients [CD14]

PROVIDER: PRJNA782259 | ENA |

REPOSITORIES: ENA

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Genome-wide DNA methylation profiling identifies epigenetic changes in CD4+ and CD14+ cells of multiple sclerosis patients [CD14]

Project description:Multiple sclerosis (MS) is a chronic autoimmune and degenerative disease of the central nervous system, which develops in genetically predisposed individuals upon exposure to environmental influences. Environmental triggers of MS, such as viral infections or smoking, were demonstrated to affect DNA methylation, and thus to involve this important epigenetic mechanism in the development of pathological processes. To identify DNA methylation hallmarks, associated with MS, we performed genome-wide DNA methylation profiling of two cell populations (CD4+ T-lymphocytes and CD14+ monocytes), collected from the same individuals (relapsing-remitting MS patients and healthy subjects), using Illumina 450K methylation arrays. We revealed significant changes in DNA methylation for both cell populations of studied groups. In CD4+ cells the majority of differentially methylated positions (DMPs) were shown to be hypomethylated, while in CD14+ cells – hypermethylated in MS patients. Noteworthy, in CD4+, but not in CD14+ cells, we found differential methylation of HLA-DRB6 gene from HLA locus, which is known to have the strongest genetic association with MS. Besides, about 20% of DMPs identified in studied cells were identical; they all had the same direction of methylation changes in both cell populations and may be involved in basic epigenetic processes occuring in MS. These findings suggest that the epigenetic mechanism of DNA methylation in immune cells contributes to MS; further studies are now required to validate these results and understand their functional significance.

2022-02-28 | GSE189256 | GEO

Genome-wide DNA methylation profiling identifies epigenetic changes in CD4+ and CD14+ cells of multiple sclerosis patients [CD4]

2022-02-28 | GSE189255 | GEO

Genome-wide DNA methylation profiling identifies epigenetic changes in CD4+ and CD14+ cells of multiple sclerosis patients [CD4]

Project description:Genome-wide DNA methylation profiling identifies epigenetic changes in CD4+ and CD14+ cells of multiple sclerosis patients [CD4]

| PRJNA782252 | ENA

Genome-wide DNA methylation profiling identifies epigenetic changes in CD4+ and CD14+ cells of multiple sclerosis patients

Project description:Genome-wide DNA methylation profiling identifies epigenetic changes in CD4+ and CD14+ cells of multiple sclerosis patients

| PRJNA782255 | ENA

Cell-Type-Specific Transcriptome of CD4+, CD8+ T cells and CD14+ monocytes in multiple sclerosis

Project description:Multiple sclerosis (MS) is an autoimmune disease of the central nervous system in which both genetic and environmental factors are thought to be involved. Genome-wide association studies revealed more than 200 risk loci, most of which harbor genes primarily expressed in immune cells. However, whether genetic differences are translated into cell-specific gene expression profiles and to what extent these are altered in MS are not well understood. To assess cell-type-specific gene expression in a large cohort of MS patients, we sequenced the whole transcriptome of sorted T cells (CD4+ and CD8+) and CD14+ monocytes from treatment-naive MS patients (n=122) and healthy subjects (n=22). Next, we performed a comprehensive analysis of the RNA sequencing dataset and identified 612 differentially expressed genes (DEGs) in CD14+ monocytes, 464 in CD4+ T cells, and 93 in CD8+ T cells. Notably, about one third (36.6%) of DEGs were non-coding RNAs, the majority of which (88.2%) were down-regulated in MS. We identified large co-expressed gene modules and cis-eQTLs with key MS genes in each cell subset. Importantly, we discovered dysregulation of NAE1, a subunit of NEDD8 activating enzyme (NAE), in CD4+ T cells which activates the neddylation pathway. Finally, we demonstrated that NAE inhibition using Pevonedistat (MLN4924) dampened disease severity in murine experimental autoimmune encephalomyelitis (EAE). Our findings provide novel insights into MS-associated gene regulation unraveling neddylation as a crucial pathway in MS pathogenesis with implications for the development of tailored disease-modifying agents.

2020-12-31 | GSE137143 | GEO

Cell-Type-Specific Transcriptome of CD4+, CD8+ T cells and CD14+ monocytes in multiple sclerosis

Project description:Cell-Type-Specific Transcriptome of CD4+, CD8+ T cells and CD14+ monocytes in multiple sclerosis

| PRJNA564629 | ENA

Dissection of multiple sclerosis genetics identifies B and CD4+ T cells as driver cell subsets

Project description:Dissection of multiple sclerosis genetics identifies B and CD4+ T cells as driver cell subsets

| PRJNA834633 | ENA

Epigenome analysis of CD4 T cells from treated and untreated patients with multiple sclerosis (MS)

Project description:Genome wide DNA methylation profiling of CD4 T cells from treated and untreated patients with multiple sclerosis. The Illumina InfiniumEPIC methylation Beadchip was used to obtain DNA methylation profiles across approximately 850,000 CpGs of CD4 T cells from patients with multiple sclerosis.

2018-04-03 | GSE112596 | GEO

Transcriptome data of multiple sclerosis patients receiving fingolimod therapy [HTA-2_0, CD14+ cells, exon level]

Project description:We analyzed the gene expression patterns of different blood cell types before and during fingolimod treatment in a group of patients with relapsing-remitting multiple sclerosis (RRMS). Affymetrix Human Transcriptome Arrays (HTA) 2.0 were used to obtain gene expression profiles of immune cell populations from 10 RRMS patients within the first 3 months of fingolimod treatment. This GEO entry provides the Affymetrix HTA 2.0 microarray data of peripheral blood CD14+ cells, preprocessed according to the exon level workflow.

2016-05-20 | GSE81603 | GEO

Transcriptome data of multiple sclerosis patients receiving fingolimod therapy [HTA-2_0, CD14+ cells, gene level]

2016-05-20 | GSE81598 | GEO

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