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Series GSE166074 Query DataSets for GSE166074
Status Public on Jan 28, 2022
Title A primed immune transcriptional program is activated in oligodendroglia in multiple sclerosis [Cut&Run IFNgvsCtr]
Organism Mus musculus
Experiment type Other
Summary Multiple sclerosis (MS) is a disease characterized by a targeted immune attack on myelin in the central nervous system (CNS). We have previously shown that oligodendrocytes (OLs), myelin producing cells in the CNS, and their precursors (OPCs), acquire disease-specific transcriptional states in MS. To understand how these alternative transcriptional programs are activated in disease, we performed single-cell assay for transposase accessible chromatin using sequencing (scATAC-seq) on the OL lineage in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS. We identified regulatory regions with increased accessibility in oligodendroglia (OLG) in EAE, some of which in the proximity of immune genes. A similar remodeling of chromatin accessibility was observed upon treatment of postnatal OPCs with interferon-gamma (IFNg), but not with dexamethasone. These changes in accessibility were not exclusive to distal enhancers, but also occurred at promoter regions, suggesting a role for promoters in mediating cell-state transitions. Notably, we found that a subset of immune genes already exhibited chromatin accessibility in OPCs ex vivo and in vivo, suggesting a primed chromatin state in OLG compatible with rapid transitions to an immune-competent state. Several primed genes presented bivalency of H3K4me3 and H3K27me3 at promoters in OPCs, with loss of H3K27me3 upon IFNg treatment. Inhibition of JMJD3/KDM6B, mediating removal of H3K27me3, led to the inability to activate these genes upon IFNg treatment. Importantly, OLGs from the adult human brain showed chromatin accessibility at immune gene loci, particularly at MHC-I pathway genes. A subset of single-nucleotide polymorphisms (SNPs) associated with MS susceptibility overlapped with these primed regulatory regions in OLG from both mouse and human CNS. Our data suggest that susceptibility for MS may involve activation of immune gene programs in OLG. These programs are under tight control at the chromatin level in OLG and may therefore constitute novel targets for immunological-based therapies for MS.
 
Overall design We have performed bulk CUT&RUN for H3K27ac, H3K27me3, H3K4me3 and Ctcf from FACS sorted Sox10GFP+ oligodendrocyte precursor cells treated with IFN-gamma fro 48 hours.
 
Contributor(s) Meijer M, Agirre E, Castelo-Branco G
Citation(s) 35093191
Submission date Feb 03, 2021
Last update date Apr 29, 2022
Contact name Eneritz Agirre
Organization name Karolinska Institutet
Department MBB
Lab Castelo-Branco, Molecular Neurobiology
Street address Solnav├Ągen 9
City Stockholm
ZIP/Postal code 17165
Country Sweden
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (21)
GSM5061444 H3K27ac_Ctr_rep1
GSM5061445 H3K27ac_IFNg_rep1
GSM5061446 Ctcf_Ctr_rep1
Relations
BioProject PRJNA699227
SRA SRP304519

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Supplementary file Size Download File type/resource
GSE166074_Ctr_Ctcf_dupmark.bam_peaks.narrowPeak.gz 982.3 Kb (ftp)(http) NARROWPEAK
GSE166074_Ctr_H3K27ac_dupmark.bam_peaks.broadPeak.gz 251.5 Kb (ftp)(http) BROADPEAK
GSE166074_Ctr_H3K27me3_dupmark.bam_peaks.broadPeak.gz 460.9 Kb (ftp)(http) BROADPEAK
GSE166074_Ctr_H3K4me3_dupmark.bam_peaks.broadPeak.gz 672.0 Kb (ftp)(http) BROADPEAK
GSE166074_IFNg_Ctcf_dupmark.bam_peaks.narrowPeak.gz 944.9 Kb (ftp)(http) NARROWPEAK
GSE166074_IFNg_H3K27ac_dupmark.bam_peaks.broadPeak.gz 463.1 Kb (ftp)(http) BROADPEAK
GSE166074_IFNg_H3K27me3_dupmark.bam_peaks.broadPeak.gz 337.6 Kb (ftp)(http) BROADPEAK
GSE166074_IFNg_H3K4me3_dupmark.bam_peaks.broadPeak.gz 686.7 Kb (ftp)(http) BROADPEAK
GSE166074_RAW.tar 3.7 Gb (http)(custom) TAR (of WIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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