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Series GSE130118 Query DataSets for GSE130118
Status Public on Feb 12, 2020
Title Genome-wide analysis of the transcriptional profile of astrocytes across EAE by CNS region in Gfap-Cre;Ribotag(f/f) mice uisng Ribotag immunoprecipitation.
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary We identify pathways regulated in astrocytes across EAE by CNS region.
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.
 
Overall design Naïve (n=3 per region); acute (n=3 cerebellum, cranial nerves; n=2 cortex, parenchyma, spinal cord); remitting (n=3 spinal cord, cerebellum, cranial nerves; n=2 cortex, parenchyma)
 
Contributor(s) Wheeler MA, Tjon EC, Quintana FJ
Citation(s) 32051591
Submission date Apr 22, 2019
Last update date Feb 28, 2020
Contact name Michael Wheeler
E-mail(s) mwheeler0@bwh.harvard.edu
Organization name Brigham and Women's Hospital
Department Neurology
Street address 60 Fenwood Rd.
City Boston
State/province MA
ZIP/Postal code 02115
Country USA
 
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (40)
GSM3732370 J1_Acute_Cortex_rep1
GSM3732371 J2_Acute_SC_rep1
GSM3732372 J3_Acute_Parenchyma_rep1
This SubSeries is part of SuperSeries:
GSE130119 MAFG-driven astrocytes promote CNS inflammation
Relations
BioProject PRJNA534023
SRA SRP193309

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
GSE130118_ribotag_STAR_readCounts_IP.txt.gz 522.0 Kb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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