Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Myelin insulation as a risk factor for axonal degeneration in autoimmune demyelinating disease

ABSTRACT: Axonal degeneration determines the clinical outcome of multiple sclerosis (MS), and is thought to result from exposure of denuded axons to immune-mediated damage. We challenge this view after finding in MS and its mouse models that myelin itself increases the risk of axons to degenerate under inflammatory conditions. We propose a model for demyelinating diseases in which for axons that remain myelinated, and thus shielded from the extracellular milieu, dependence from oligodendroglial support turns fatal in an autoimmune disease environment.

ORGANISM(S): Mus musculus

PROVIDER: GSE222063 | GEO | 2023/05/02

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Rattus norvegicus

Project description:Transcriptome of myelinated motor axons

| PRJNA598237 | ENA

The X-Linked Intellectual Disability gene, ZDHHC9, is important for oligodendrocyte maturation and myelin formation

Project description:Two percent of all patients with X-linked intellectual disability (XLID) exhibit loss-of-function mutations in the palmitoylating enzyme, ZDHHC9. One of the main anatomical deficits observed in these patients is a decrease in corpus callosum volume and a disruption of white matter integrity. We demonstrated that ablation of Zdhhc9 in mice substantially impairs the maturation of oligodendrocytes, resulting in fewer mature, myelinating oligodendrocytes, higher numbers of oligodendrocyte progenitor cells and a decrease in the density of myelinated axons. Ultrastructural analysis of the remaining myelinated axons in the corpus callosum revealed further disruptions in myelin integrity. RNA sequencing and proteomic analyses revealed a concomitant decrease in the expression of genes and proteins involved in lipid metabolism, cholesterol synthesis and myelin compaction. These results reveal a previously underappreciated and fundamental role for ZDHHC9 and protein palmitoylation in regulating oligodendrocyte differentiation and myelinogenesis and provide mechanistic insights into the deficits observed in white matter volume in patients with mutations in ZDHHC9.

2023-08-21 | GSE236665 | GEO

The X-Linked Intellectual Disability gene, ZDHHC9, is important for oligodendrocyte maturation and myelin formation

Project description:Two percent of all patients with X-linked intellectual disability (XLID) exhibit loss-of-function mutations in the palmitoylating enzyme, ZDHHC91,2. One of the main anatomical deficits observed in these patients is a decrease in corpus callosum volume and a disruption of white matter integrity. We demonstrated that ablation of Zdhhc9 in mice substantially impairs the maturation of ligodendrocytes, resulting in fewer mature, myelinating oligodendrocytes, higher numbers of oligodendrocyte progenitor cells and a decrease in the density of myelinated axons. Ultrastructural analysis of the remaining myelinated axons in the corpus callosum revealed further disruptions in myelin integrity. RNA sequencing and proteomic analyses revealed a concomitant decrease in the expression of genes and proteins involved in lipid metabolism, cholesterol synthesis and myelin compaction. These results reveal a previously underappreciated and fundamental role for ZDHHC9 and protein palmitoylation in regulating oligodendrocyte differentiation and myelinogenesis and provide mechanistic insights into the deficits observed in white matter volume in patients with mutations in ZDHHC9.

2023-06-30 | MSV000092318 | MassIVE

The transcriptome of central nervous system myelin

Project description:Rapid nerve conduction in the CNS is facilitated by the insulation of axons with myelin, a specialized oligodendroglial compartment distant from the cell body. Myelin is turned over and adapted throughout life; however, the molecular and cellular basis of myelin dynamics is not well understood. Hypothesizing that only a fraction of all myelin-related mRNAs has been identified so far, we subjected myelin biochemically purified from mouse brains at various ages to RNA sequencing. We find a surprisingly large pool of transcripts abundant and/or enriched in myelin. Furthermore, a comprehensive analysis showed that the myelin transcriptome is closely related to the myelin proteome but clearly distinct from the transcriptomes of oligodendrocytes and brain tissues, suggesting that the incorporation of mRNAs into the myelin compartment is highly selective. The mRNA-pool in myelin displays maturation-dependent dynamic changes of composition, abundance, and functional associations; however ageing-dependent changes after 6 months of age were minor. We suggest that this transcript pool provides a basis for the local modulation of myelin turnover and adaptation, i.e. in the individual internode. A light-weight membrane fraction enriched for myelin was purified from mouse brains as described previously (Jahn et al., Neuromethods, 2013). For RNA-Seq, RNA was isolated from myelin of mice from indicated ages.

2016-06-24 | E-GEOD-78151 | biostudies-arrayexpress

The transcriptome of central nervous system myelin

Project description:Rapid nerve conduction in the CNS is facilitated by the insulation of axons with myelin, a specialized oligodendroglial compartment distant from the cell body. Myelin is turned over and adapted throughout life; however, the molecular and cellular basis of myelin dynamics is not well understood. Hypothesizing that only a fraction of all myelin-related mRNAs has been identified so far, we subjected myelin biochemically purified from mouse brains at various ages to RNA sequencing. We find a surprisingly large pool of transcripts abundant and/or enriched in myelin. By bioinformatic comparison, the myelin transcriptome is closely related to the myelin proteome but clearly distinct from the transcriptomes of oligodendrocytes and brain tissues, suggesting that the incorporation of mRNAs into the myelin compartment is highly selective. The mRNA-pool in myelin displays maturation-dependent dynamic changes of composition, abundance, and functional associations; however ageing-dependent changes after 6 months of age were minor. We suggest that this transcript pool provides a basis for the local modulation of myelin turnover and adaptation, i.e. in the individual internode.

2016-12-31 | GSE76458 | GEO

The transcriptome of central nervous system myelin

2016-06-24 | GSE78151 | GEO

Loss of Myelin Basic Protein Function Triggers Myelin Breakdown in Models of Demyelinating Diseases.

Project description: Not available

| S-EPMC4949381 | biostudies-literature

PAD2-mediated citrullination contributes to efficient oligodendrocyte differentiation and myelination

Project description:Citrullination, the deimination of arginine residues into citrulline, has been implicated in the aetiology of several diseases. In multiple sclerosis (MS), citrullination is thought to be a major driver of pathology, through hypercitrullination and destabilization of myelin. As such, inhibition of citrullination has been suggested as a therapeutical strategy for MS. Here we show that citrullination by peptidylarginine deiminase 2 (PADI2) is in contrast required for normal oligodendrocyte differentiation, myelination and motor function. We identify several targets for PADI2, including not only myelin-related proteins, but also several chromatin-associated proteins, implicating PADI2 in epigenetic regulation. Accordingly, we observe that PADI2 inhibition and its knockdown affect chromatin accessibility and prevent the upregulation of genes involved in oligodendrocyte differentiation. Moreover, mice lacking PADI2, display motoric dysfunction and a decreased number of myelinated axons in the corpus callosum. Our study demonstrates that citrullination is required for oligodendrocyte lineage progression and myelination and thus its targeted activation in the oligodendrocyte lineage might be beneficial in the context of remyelination in diseases as MS.

2019-04-23 | GSE115929 | GEO

Myelin Oligodendrocyte Glycoprotein: Deciphering a Target in Inflammatory Demyelinating Diseases.

Project description: Not available

| S-EPMC5420591 | biostudies-literature

Primary spinal OPC culture system from adult zebrafish to study oligodendrocyte differentiation in vitro

Project description:Endogenous oligodendrocyte progenitor cells (OPCs) are a promising target to improve functional recovery after spinal cord injury (SCI) by remyelinating denuded, and therefore vulnerable, axons. Demyelination is the result of a primary insult and secondary injury, leading to conduction blocks and long-term degeneration of the axons, which subsequently can lead to the loss of their neuron. In response to SCI, dormant OPCs can be activated and subsequently start to proliferate and differentiate into mature myelinating oligodendrocytes (OLs). Therefore, researchers strive to control OPC responses, and utilize small molecule screening approaches in order to identify mechanisms of OPC activation, proliferation, migration and differentiation.

2017-09-05 | GSE100821 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data