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Items: 4

1.

MAFG-driven astrocytes promote CNS inflammation

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.
Organism:
Mus musculus; Homo sapiens
Type:
Methylation profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing; Other; Expression profiling by high throughput sequencing
5 related Platforms
163 Samples
Download data: BEDGRAPH, CSV, TXT
Series
Accession:
GSE130119
ID:
200130119
2.

Genome-wide analysis of MAFG binding in astrocytes during EAE [ChIP-seq]

(Submitter supplied) We report MAFG recruitment to ARE elements in astrocytes during EAE compared to naïve mice Multiple sclerosis (MS) is an autoimmune neurologic disease leading to demyelination and neurologic dysfunction controlled by both genetic and environmental factors. In addition to CNS-infiltrating immune cells, CNS-resident cells, such as astrocytes, are thought to play an important role in MS pathogenesis. However, a comprehensive understanding of the extent to which gene expression is disrupted in astrocytes is not known. Here, we implement single-cell RNA sequencing, in vivo genetic perturbations, cell-specific RNA profiling by Ribotag, as well as single-cell RNA sequencing of human MS patient samples to identify a transcriptional regulatory network in astrocytes that controls the pathogenesis of EAE and potentially, MS. We defined an astrocyte subpopulation characterized by expression of the small Maf protein, MAFG, which represses NRF2-driven antioxidant mechanisms and promotes EAE pathogenesis. Mechanistically, MAFG suppresses NRF2-dependent antioxidant genetic programs by cooperating with its cofactor, MAT2a, to promote DNA methylation in the context of CNS inflammation, which in turn increases pathogenic signaling processes in astrocytes. MAFG/MAT2a astrocytes are controlled by GM-CSF signaling, which drives EAE pathogenesis and MAFG expression. MAFG is activated in astrocytes derived from MS patients, which are characterized by DNA methylation programs, pro-inflammatory signaling processes including GM-CSF signaling, and repressed NRF2 activation. Together, these data create a transcriptional and epigenetic framework to analyze CNS inflammation in MS and may provide new therapeutic targets.
Organism:
Mus musculus
Type:
Genome binding/occupancy profiling by high throughput sequencing
Platform:
GPL21103
11 Samples
Download data: NARROWPEAK
Series
Accession:
GSE129607
ID:
200129607
3.

Illumina HiSeq 4000 (Mus musculus)

Platform
Accession:
GPL21103
ID:
100021103
4.

EAE_MAFG_Input_Replicate1

Organism:
Mus musculus
Source name:
EAE_Input_astrocytes
Platform:
GPL21103
Series:
GSE129607 GSE130119
Download data
Sample
Accession:
GSM3717005
ID:
303717005
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