Rattus norvegicus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA215855 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The molecular basis of CNS myelin regeneration (remyelination) is poorly understood. Here we generate a comprehensive transcriptional profile of the separate stages of spontaneous remyelination following focal demyelination in the rat CNS. White matter tracts in the rat caudal cerebellar peduncles were focally demyelinated using 0.1% ethidium bromide, the lesions were isolated using laser capture microdissection at 5, 14 and 28 days postlesion, followed by RNA extraction and Illumina beadarray analysis of differentially expressed transcripts. We found transcripts encoding retinoid acid receptor RXR-gamma is highly differentially expressed during remyelination, and that oligodendrocyte lineage cells express RXR-gamma in rat tissues undergoing remyelination and in active and remyelinated MS lesions. RXR-gamma knockdown by RNA interference or RXR-specific antagonists severely inhibit oligodendrocyte differentiation in culture. In RXR-gamma deficient mice, adult oligodendrocyte precursor cells efficiently repopulate lesions following demyelination, but display delayed differentiation into mature oligodendrocytes. Administration of the RXR agonist 9-cis-retinoic acid to demyelinated cerebellar slice cultures and to aged rats following demyelination results in more remyelinated axons. RXR-gamma is therefore a positive regulator of endogenous oligodendrocyte precursor cell differentiation and remyelination, and may be a pharmacological target for CNS regenerative therapy. 9 Samples analysed, 3 different time points each with 3 biological replicates.
2010-10-22 | E-GEOD-24821 | biostudies-arrayexpress
Project description:Myelin aging is a driving force of CNS aging, and age-dependent declined efficiency of remyelination caused by impaired differentiation capacity of aged oligodendrocyte precursor cell (OPC) is a major cause of demyelinated diseases. Revealing how differentiation capacity of aged OPC is affected metabolically holds the key to find new way to rejuvenate the aged OPC. Here we screened out that NAD+ is one of the top metabolites impaired in premature aging OPC. Supplementing β-nicotinamide mononucleotide (β-NMN), an immediate NAD+ precursor, delays CNS myelin aging, promotes differentiation of aged OPC, and therapeutically and preventively rejuvenates remyelination in the aged CNS both ultra-structurally and functionally. To explore the molecular mechanisms underlying the enhancing remyelination by NAD+ supplementation, using LC-MS we investigated the changes of proteome differentially regulated by NAD+ or DMSO in cultured OPC from P0 rat brain.
2020-10-18 | PXD022046 |
Project description:The molecular basis of CNS myelin regeneration (remyelination) is poorly understood. Here we generate a comprehensive transcriptional profile of the separate stages of spontaneous remyelination following focal demyelination in the rat CNS. White matter tracts in the rat caudal cerebellar peduncles were focally demyelinated using 0.1% ethidium bromide, the lesions were isolated using laser capture microdissection at 5, 14 and 28 days postlesion, followed by RNA extraction and Illumina beadarray analysis of differentially expressed transcripts. We found transcripts encoding retinoid acid receptor RXR-gamma is highly differentially expressed during remyelination, and that oligodendrocyte lineage cells express RXR-gamma in rat tissues undergoing remyelination and in active and remyelinated MS lesions. RXR-gamma knockdown by RNA interference or RXR-specific antagonists severely inhibit oligodendrocyte differentiation in culture. In RXR-gamma deficient mice, adult oligodendrocyte precursor cells efficiently repopulate lesions following demyelination, but display delayed differentiation into mature oligodendrocytes. Administration of the RXR agonist 9-cis-retinoic acid to demyelinated cerebellar slice cultures and to aged rats following demyelination results in more remyelinated axons. RXR-gamma is therefore a positive regulator of endogenous oligodendrocyte precursor cell differentiation and remyelination, and may be a pharmacological target for CNS regenerative therapy.
2010-10-22 | GSE24821 | GEO
Project description:Retinoid X receptor gamma signaling accelerates CNS remyelination
| PRJNA132203 | ENA
Project description:Transcriptome outcome of oligodendrocyte precursor cells following VCAM1 knockdown
| PRJNA342795 | ENA
Project description:The progressive loss of CNS myelin in patients with multiple sclerosis (MS) has been proposed to result from the combined effects of damage to oligodendrocytes and failure of remyelination. A common feature of demyelinated lesions is the presence of oligodendrocyte precursors (OLPs) blocked at a premyelinating stage. However, the mechanistic basis for inhibition of myelin repair is incompletely understood. To identify novel regulators of OLP differentiation, potentially dysregulated during repair, we performed a genome-wide screen of 1040 transcription factor-encoding genes expressed in remyelinating rodent lesions. We report that M-bM-^HM-<50 transcription factor-encoding genes show dynamic expression during repair and that expression of the Wnt pathway mediator Tcf4 (aka Tcf7l2) within OLPs is specific to lesionedM-bM-^@M-^Tbut not normalM-bM-^@M-^Tadult white matter. We report that M-NM-2-catenin signaling is active during oligodendrocyte development and remyelination in vivo. Moreover, we observed similar regulation of Tcf4 in the developing human CNS and lesions of MS. Data mining revealed elevated levels of Wnt pathway mRNA transcripts and proteins within MS lesions, indicating activation of the pathway in this pathological context. We show that dysregulation of WntM-bM-^@M-^SM-NM-2-catenin signaling in OLPs results in profound delay of both developmental myelination and remyelination, based on (1) conditional activation of M-NM-2-catenin in the oligodendrocyte lineage in vivo and (2) findings from APCMin mice, which lack one functional copy of the endogenous Wnt pathway inhibitor APC. Together, our findings indicate that dysregulated WntM-bM-^@M-^SM-NM-2-catenin signaling inhibits myelination/remyelination in the mammalian CNS. Evidence of Wnt pathway activity in human MS lesions suggests that its dysregulation might contribute to inefficient myelin repair in human neurological disorders. 12 samples total. Two variables in the experiment: genotype (wild type or Olig2cre/DA-Cat) and Developmental stage (Day 4 or Day 15). 4 phenotypes in total with 3 biological replicates for each phenotype.
2009-12-10 | E-GEOD-19403 | biostudies-arrayexpress
Project description:Multiple Sclerosis (MS) is a neuroinflammatory disease characterized by demyelinated lesions in the CNS. Remyelination in MS is variable between individuals and tends to become less efficient with aging. Microglia and astrocytes are known to have critical roles in MS pathogenesis, but to what extent their activity is altered by remyelination failure remains unclear. To determine the effects of demyelination on neuroinflammation, we use two mouse models that genetically ablate myelinating oligodendrocytes. We use the Plp1-CreERT mouse line crossed with the Myrf fl/fl mouse line to induce genetic demyelination throughout the CNS following adult tamoxifen administration. Subsequent remyelination is mediated by the proliferation and differentiation of oligodendrocyte precursor cells (OPCs) to newly formed oligodendrocytes. To assess the consequences of remyelination failure, we deleted Myrf from both mature oligodendrocytes and OPCs using Myrf fl/fl; Sox10-CreERT mice, which both induces demyelination and impairs subsequent remyelination. To characterize the glial cells in these demyelinated mice, we performed single-nucleus RNA-sequencing (snRNAseq) of optic nerves at peak demyelination, generating an atlas of non-neuronal cells including oligodendrocyte lineage cells, astrocytes, microglia, endothelial cells, pericytes, arachnoid barrier cells, vascular and leptomeningeal cells.
2024-09-12 | GSE243788 | GEO
Project description:Transcriptome response to endoplasmic reticulum stress in rat oligodendrocyte precursor cells
| PRJNA322543 | ENA
Project description:We used transcription-profiling to identify mitogen-activated protein kinase (Mapk) signaling as an important regulator involved in the differentiation of oligodendrocyte progenitor cells (OPCs) into oligodendrocytes. We show in tissue culture that activation of Mapk signaling by elevation of intracellular levels of cAMP using administration of either dibutyryl-cAMP or inhibitors of the cAMP-hydrolyzing enzyme phosphodiesterase-4 (Pde4) enhances OPC differentiation. Finally, we demonstrate that systemic delivery of a Pde4 inhibitor leads to enhanced differentiation of OPCs within focal areas of toxin-induced demyelination and a consequent acceleration of remyelination.
2013-08-29 | GSE50042 | GEO
Project description: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.
2017-04-21 | GSE80439 | GEO