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Series GSE118451 Query DataSets for GSE118451
Status Public on Apr 29, 2019
Title Gene expression in oligodendrocytes during remyelination reveals cholesterol homeostasis as a therapeutic target in multiple sclerosis.
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Regional differences in neurons, astrocytes, oligodendrocytes, and microglia exist in the brain during health, and regional differences in the transcriptome may occur for each cell type during neurodegeneration. Multiple sclerosis (MS) is multifocal, and regional differences in the astrocyte transcriptome occur in experimental autoimmune encephalomyelitis (EAE), an MS model. MS and EAE are characterized by inflammation, demyelination, and axonal damage, with minimal remyelination. Here, RNA-sequencing analysis of MS tissues from six brain regions suggested a focus on oligodendrocyte lineage cells (OLCs) in corpus callosum. Olig1-RiboTag mice were used to determine the translatome of OLCs in vivo in corpus callosum during the remyelination phase of a chronic cuprizone model with axonal damage. Cholesterol-synthesis gene pathways dominated as the top up-regulated pathways in OLCs during remyelination. In EAE, remyelination was induced with estrogen receptor-β (ERβ) ligand treatment, and up-regulation of cholesterol-synthesis gene expression was again observed in OLCs. ERβ-ligand treatment in the cuprizone model further increased cholesterol synthesis gene expression and enhanced remyelination. Conditional KOs of ERβ in OLCs demonstrated that increased cholesterol-synthesis gene expression in OLCs was mediated by direct effects in both models. To address this direct effect, ChIP assays showed binding of ERβ to the putative estrogen-response element of a key cholesterol-synthesis gene (Fdps). As fetal OLCs are exposed in utero to high levels of estrogens in maternal blood, we discuss how remyelinating properties of estrogen treatment in adults during injury may recapitulate normal developmental myelination through targeting cholesterol homeostasis in OLCs.
Overall design The mice expressing HA-tagged ribosomal protein RPL22 in oligodendrocytes were generated by crossing RiboTag mice with Olig1-Cre mice. Oligodendrocyte specific RNA was isolated as the co-immunoprecipitation with anti-HA antibody.
Citation(s) 31040210
Submission date Aug 13, 2018
Last update date May 24, 2019
Contact name Yuichiro Itoh
Phone 3102068999
Organization name UCLA
Department Neurology
Street address 635 Charles E. Young Drive South
City Los Angeles
State/province California
ZIP/Postal code 90095
Country USA
Platforms (1)
GPL21493 Illumina HiSeq 3000 (Mus musculus)
Samples (6)
GSM3330413 Vehicle_24
GSM3330414 Vehicle_26
GSM3330415 Vehicle_27
BioProject PRJNA485694
SRA SRP157610

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Supplementary file Size Download File type/resource
GSE118451_Olig1.RiboTag_rawcounts.txt.gz 328.8 Kb (ftp)(http) TXT
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Processed data are available on Series record

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