Human Gene Set: GOBERT_CORE_OLIGODENDROCYTE_DIFFERENTIATION

For the Mouse gene set with the same name, see GOBERT_CORE_OLIGODENDROCYTE_DIFFERENTIATION

Standard name GOBERT_CORE_OLIGODENDROCYTE_DIFFERENTIATION
Systematic name M2370
Brief description Oligodendrocyte core differentiation genes: up-regulated in Oli-neo cells (oligodendroglial precursor) at 10 h after treatment with PD174265, dexamethasone or isotretinoin [PubChem=4709] [PubChem=5743] [PubChem=5282379].
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
      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,Hooft van Huijsduijnen R
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Organism Mus musculus
Contributed by Arthur Liberzon (MSigDB Team)
Source platform AFFY_Mouse430
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Version history 3.1: First introduced

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