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Series GSE154175 Query DataSets for GSE154175
Status Public on May 21, 2021
Title A primed immune transcriptional program is activated in oligodendroglia in multiple sclerosis [SCATAC_10X]
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
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 used 3 samples of EAE (MS mouse model) and 4 control samples of mouse spinal cord tissue and sequence them using 10X Genomics scATAC-seq v1 Chemistry to study the chromatin states of Oligodendroglia during disease.
 
Contributor(s) Meijer M, Agirre E, Kabbe M, van Tuijn CA, Heskol A, Falcao AM, Corces MR, Montine TJ, Chen X, Chang HY, Castelo-Branco G
Citation(s) 35093191
Submission date Jul 10, 2020
Last update date May 06, 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 (7)
GSM4665461 EAE1
GSM4665462 Ctr1
GSM4665463 EAE2
This SubSeries is part of SuperSeries:
GSE166179 A primed immune transcriptional program is activated in oligodendroglia in multiple sclerosis
Relations
BioProject PRJNA645368
SRA SRP271246

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE154175_MOL12_EAE_Celltypes_10XEAE_peaks_RND.wig.gz 24.4 Mb (ftp)(http) WIG
GSE154175_MOL2_Ctr_RND1_Celltypes_10XEAE_peaks_RND.wig.gz 24.1 Mb (ftp)(http) WIG
GSE154175_MOL3_EAE_Celltypes_10XEAE_peaks_RND.wig.gz 17.4 Mb (ftp)(http) WIG
GSE154175_MOL56_Ctr_RND3_Celltypes_10XEAE_peaks_RND.wig.gz 23.6 Mb (ftp)(http) WIG
GSE154175_Meijer_Agirre_scATAC_metadata_umap.csv.gz 1017.4 Kb (ftp)(http) CSV
GSE154175_MiGl_RND1_Celltypes_10XEAE_peaks_RND.wig.gz 35.9 Mb (ftp)(http) WIG
GSE154175_OPC_Ctr_RND1_Celltypes_10XEAE_peaks_RND.wig.gz 25.8 Mb (ftp)(http) WIG
GSE154175_OPC_EAE_RND1_Celltypes_10XEAE_peaks_RND.wig.gz 34.8 Mb (ftp)(http) WIG
GSE154175_RAW.tar 488.3 Mb (http)(custom) TAR (of CSV, H5)
GSE154175_filtered_peak_bc_matrix.h5 114.9 Mb (ftp)(http) H5
GSE154175_fragments.tsv.gz 2.2 Gb (ftp)(http) TSV
GSE154175_peaks.bed.gz 795.2 Kb (ftp)(http) BED
GSE154175_scATAC_EAECtrl_GEO.rds.gz 754.1 Mb (ftp)(http) RDS
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Raw data are available in SRA
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Processed data provided as supplementary file

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