Transcriptomics

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A primed immune transcriptional programme is activated in oligodendroglia in multiple sclerosis [ATAC-Seq and RNA-Seq II]


ABSTRACT: Multiple sclerosis (MS) is characterized by a targeted attack on oligodendroglia (OLG) and myelin by immune cells, which are thought to be the main drivers of MS susceptibility. We found that immune genes exhibit a primed chromatin state in single mouse and human OLG in a non-disease context, compatible with transitions to immune-competent states in MS. We identified transcription factors as BACH1 and STAT1 involved in immune gene regulation in oligodendrocyte precursor cells (OPCs). A subset of immune genes present bivalency of H3K4me3/H3K27me3 in OPCs, with Polycomb inhibition leading to their increased activation upon interferon-gamma (IFN) treatment. Some MS susceptibility single-nucleotide polymorphisms (SNPs) overlap with these regulatory regions in mouse and human OLG. Treatment of mouse OPCs with IFN leads to chromatin architecture remodeling at these loci and altered expression of interacting genes. Thus, susceptibility for MS may involve OLG, which therefore constitute novel targets for immunological-based therapies for MS.

ORGANISM(S): Homo sapiens

PROVIDER: GSE193240 | GEO | 2022/01/28

REPOSITORIES: GEO

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