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DNA methylation profiles of four immune cell types from MS patients and healthy controls

ABSTRACT: DNA methylation profiles of four immune cell types from MS patients and healthy controls

PROVIDER: PRJNA727170 | ENA |

REPOSITORIES: ENA

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DNA methylation profiles of four immune cell types from MS patients and healthy controls

Project description:How epigenetic changes contribute to MS pathogenesis is still poorly understood. Therefore, we conducted a comprehensive analysis of genome-wide DNA methylation patterns in four immune cell populations isolated from MS patients at clinical disease onset. We also performed parallel transcriptome analysis in B cells to better understand the functional consequences of the DNA methylation changes in MS.

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Transcriptome profiles of B cells from MS patients and healthy controls

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Project description:In order to better understand the functional properties of this type of cells under different circumstances, we integrated the single-cell RNA-seq data of peripheral blood CD8+ T cells from healthy subjects, MS patients and COVID-19 patients generated from the 10X Genomics platform using the Seurat package. KIR+CD8+ T cells from different conditions (healthy, MS, and COVID-19) formed a distinct cluster with high expression of effector genes (GZMB and PRF1) as well as KIR transcripts. These findings reveal the commonality of KIR+CD8+ T cells across physiological and diseased status as well as their uniqueness relative to other CD8+ T cells.

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Combining evidence from four immune cell types identifies DNA methylation patterns that implicate functionally distinct pathways during Multiple Sclerosis progression (CD8+ T cells)

Project description:Background Multiple Sclerosis (MS) is a chronic inflammatory disease and a leading cause of progressive neurological disability among young adults. DNA methylation, which intersects genes and environment to control cellular functions on a molecular level, may provide insights into MS pathogenesis. Methods We measured DNA methylation in CD4+ T cells (n=31), CD8+ T cells (n=28), CD14+ monocytes (n=35) and CD19+ B cells (n=27) from relapsing-remitting (RRMS), secondary progressive (SPMS) patients and healthy controls (HC) using Infinium HumanMethylation450 arrays. Monocyte (n=25) and whole blood (n=275) cohorts were used for validations. Findings B cells from MS patients displayed most significant differentially methylated positions (DMPs), followed by monocytes, while only few DMPs were detected in T cells. We implemented a non-parametric combination framework (omicsNPC) to increase discovery power by combining evidence from all four cell types. Identified shared DMPs co-localized at MS risk loci and clustered into distinct groups. Functional exploration of changes discriminating RRMS and SPMS from HC implicated lymphocyte signaling, T cell activation and migration. SPMS-specific changes, on the other hand, implicated myeloid cell functions and metabolism. Interestingly, neuronal and neurodegenerative genes and pathways were also specifically enriched in the SPMS cluster. Interpretation We utilized a statistical framework (omicsNPC) that combines multiple layers of evidence to identify DNA methylation changes that provide new insights into MS pathogenesis in general, and disease progression, in particular.

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Combining evidence from four immune cell types identifies DNA methylation patterns that implicate functionally distinct pathways during Multiple Sclerosis progression (CD4+ T cells)

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Gene expression data: Plasmacytoid dendritic cells (pDCs) of healthy donors and MS patientes before and after IFN beta treatment

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