Gene Set: GOBERT_OLIGODENDROCYTE_DIFFERENTIATION_DN

Standard name GOBERT_OLIGODENDROCYTE_DIFFERENTIATION_DN
Systematic name M2369
Brief description Genes down-regulated during differentiation of Oli-Neu cells (oligodendroglial precursor) in response to PD174265 [PubChem=4709].
Full description or abstract Inadequate remyelination of brain white matter lesions has been associated with a failure of oligodendrocyte precursors to differentiate into mature, myelin-producing cells. In order to better understand which genes play a critical role in oligodendrocyte differentiation, we performed time-dependent, genome-wide gene expression studies of mouse Oli-neu cells as they differentiate into process-forming and myelin basic protein-producing cells, following treatment with three different agents. Our data indicate that different inducers activate distinct pathways that ultimately converge into the completely differentiated state, where regulated gene sets overlap maximally. In order to also gain insight into the functional role of genes that are regulated in this process, we silenced 88 of these genes using small interfering RNA and identified multiple repressors of spontaneous differentiation of Oli-neu, most of which were confirmed in rat primary oligodendrocyte precursors cells. Among these repressors were CNP, a well-known myelin constituent, and three phosphatases, each known to negatively control mitogen-activated protein kinase cascades. We show that a novel inhibitor for one of the identified genes, dual-specificity phosphatase DUSP10/MKP5, was also capable of inducing oligodendrocyte differentiation in primary oligodendrocyte precursors. Oligodendrocytic differentiation feedback loops may therefore yield pharmacological targets to treat disease related to dysfunctional myelin deposition.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 19139271   Authors: Gobert RP,Joubert L,Curchod ML,Salvat C,Foucault I,Jorand-Lebrun C,Lamarine M,Peixoto H,Vignaud C,Frémaux C,Jomotte T,Françon B,Alliod C,Bernasconi L,Abderrahim H,Perrin D,Bombrun A,Zanoguera F,Rommel C,Huijsduijnen van Hooft R
Exact source Suppl. file 2: cluster 3
Related gene sets (show 2 additional gene sets from the source publication)

(show 154 gene sets from the same authors)
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Organism Mus musculus
Contributed by Arthur Liberzon (Broad Institute)
Source platform Mouse430_2
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Compendia expression profiles Human tissue compendium (Novartis)
NCI-60 cell lines (National Cancer Institute)
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Version history 3.1: First introduced

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