Transcriptomics,Genomics

Dataset Information

160

MiR-219 Cooperates with miR-338 in Myelination and Promotes Myelin Repair in the CNS


ABSTRACT: microRNAs (miRNAs) have been implicated in oligodendrogenesis and demyelinating diseases; however, identification of individual miRNAs responsible has remained elusive. Through targeted mutagenesis, we find that miR-219 is required for proper oligodendrocyte differentiation and myelination in vivo. Deletion of miR-338 together with miR-219 further exacerbates hypomyelination phenotypes. Temporally specific ablation reveals a critical role for miR-219 in oligodendrocyte remyelination after demyelination, while overexpression of miR-219 promotes precocious oligodendrocyte maturation and myelin regeneration. Accordingly, administration of miR-219 mimics to lysolecithin-induced demyelinating lesions in the murine spinal cord and brain enhances myelin restoration. Through integrating analyses of transcriptome profiling and biotin-affinity miRNA pull-down, we identify a set of stage-specific targets of miR-219, including Etv5 and Lingo1, as oligodendrocyte differentiation inhibitors. Inhibiting Etv5 and Lingo1 leads to a partial rescue of differentiation defects observed in miR-219-mutant OLs in vitro. Together, our findings identify context-specific miRNA-regulated checkpoints that control CNS myelinogenesis and myelin repair. Overall design: 4 RNA-Seq samples from P12 optic nerves of Ctrl and miR-219 dCKO mice (duplicates, Ctrl and dCKO); 4 RNA-Seq samples from rat OPC with Ctrl or miR-219 mimic transduction (duplicates, Ctrl and miR-219 mimic); 4 RNA-Seq samples from rat iOL with Ctrl or miR-219 mimic transduction (duplicates, Ctrl and miR-219 mimic); and 2 RNA-Seq samples of biotin-miR-219 pull down from rat OPC (ctrl and miR-219 pull down).

INSTRUMENT(S): Illumina HiSeq 2000 (Mus musculus)

SUBMITTER: Richard Lu 

PROVIDER: GSE80439 | GEO | 2017-04-21

SECONDARY ACCESSION(S): PRJNA318906

REPOSITORIES: GEO

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Publications


A lack of sufficient oligodendrocyte myelination contributes to remyelination failure in demyelinating disorders. miRNAs have been implicated in oligodendrogenesis; however, their functions in myelin regeneration remained elusive. Through developmentally regulated targeted mutagenesis, we demonstrate that miR-219 alleles are critical for CNS myelination and remyelination after injury. Further deletion of miR-338 exacerbates the miR-219 mutant hypomyelination phenotype. Conversely, miR-219 overex  ...[more]

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