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GEO help: Mouse over screen elements for information. |
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| 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
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| 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.
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| 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.
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| Contributor(s) |
Meijer M, Agirre E, Castelo-Branco G |
| Citation(s) |
35093191 |
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| Submission date |
Feb 03, 2021 |
| Last update date |
Apr 29, 2022 |
| Contact name |
Eneritz Agirre |
| Organization name |
Karolinska Institutet
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| Department |
MBB
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| Lab |
Castelo-Branco, Molecular Neurobiology
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| Street address |
Solnavägen 9
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| City |
Stockholm |
| ZIP/Postal code |
17165 |
| Country |
Sweden |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (21)
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| Relations |
| BioProject |
PRJNA699227 |
| SRA |
SRP304519 |
| 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 Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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