GSE129609 Genome-wide analysis of the transcriptional profile of the CNS during EAE in B6 mice by scRNA-seq [scRNA-seq]

Contributors : Michael A Wheeler ; Emily C Tjon ; Francisco J Quintana ; Zhaorong LiSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusWe identify cellular heterogeneity during EAE in B6 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 expressi...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research