Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Cell type specificity of intralocus interactions reveals oligodendrocyte intrinsic mechanisms for multiple sclerosis [RNA-Seq]

ABSTRACT: Cell type specificity of intralocus interactions reveals oligodendrocyte intrinsic mechanisms for multiple sclerosis [RNA-Seq]

PROVIDER: PRJNA595888 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Cell type specificity of intralocus interactions reveals oligodendrocyte intrinsic mechanisms for multiple sclerosis

Project description:Cell type specificity of intralocus interactions reveals oligodendrocyte intrinsic mechanisms for multiple sclerosis

| PRJNA595883 | ENA

Cell type specificity of intralocus interactions reveals oligodendrocyte intrinsic mechanisms for multiple sclerosis [ChIP-Seq]

Project description:Cell type specificity of intralocus interactions reveals oligodendrocyte intrinsic mechanisms for multiple sclerosis [ChIP-Seq]

| PRJNA595890 | ENA

Cell type specificity of intralocus interactions reveals oligodendrocyte intrinsic mechanisms for multiple sclerosis [RNA-Seq]

Project description:Multiple sclerosis (MS) is an autoimmune disease characterized by attack on oligodendrocytes within the central nervous system (CNS). Despite widespread use of immunomodulatory therapies, patients face progressive disability due to failure of myelin regeneration and loss of neurons, suggesting additional cellular pathologies. Here, we describe a general approach for identifying specific cell types in which a disease allele exerts a pathogenic effect. Applying this approach to MS risk loci, we pinpoint likely pathogenic cell types for 70%. In addition to T cell loci, we unexpectedly identified myeloid and CNS-specific risk loci, including two sites that dysregulate transcriptional pause release in oligodendrocytes. Functional studies demonstrated inhibition of transcriptional elongation is a dominant pathway blocking oligodendrocyte maturation. Furthermore, pause release factors are frequently dysregulated in MS brain tissue and are associated with white matter microstructure. These data implicate cell-intrinsic aberrations outside of the immune system and suggest new avenues for therapeutic development.

2020-12-06 | GSE142085 | GEO

Cell type specificity of intralocus interactions reveals oligodendrocyte intrinsic mechanisms for multiple sclerosis [ChIP-Seq]

2020-12-06 | GSE142084 | GEO

Altered oligodendrocyte heterogeneity in Multiple sclerosis.

Project description:Altered oligodendrocyte heterogeneity in Multiple sclerosis.

| PRJNA484965 | ENA

Cell type specificity of intralocus interactions reveals oligodendrocyte intrinsic mechanisms for multiple sclerosis

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-12-06 | GSE142086 | GEO

Oligodendrocyte intrinsic miR-27a controls myelination and remyelination

Project description:Oligodendrocyte intrinsic miR-27a controls myelination and remyelination

| PRJNA558362 | ENA

Patient iPSC models reveal glia-intrinsic phenotypes in multiple sclerosis

Project description:Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease of the central nervous system (CNS), resulting in neurological disability that worsens over time. While progress has been made in defining the immune system’s role in MS pathophysiology, the contribution of intrinsic CNS-cell dysfunction remains unclear. Here, we generated a collection of iPSC lines from people with MS spanning diverse clinical subtypes and differentiated them into glia-enriched cultures. Using single-cell transcriptomic profiling and orthogonal analyses, we observed several distinguishing characteristics of MS cultures pointing to glia-intrinsic disease mechanisms. We found that primary progressive MS-derived cultures contained fewer oligodendrocytes. Moreover, MS-derived oligodendrocyte lineage cells and astrocytes showed increased expression of immune and inflammatory genes, matching those of glia from MS postmortem brains. Thus, iPSC-derived MS models provide a unique platform for dissecting glial contributions to disease phenotypes independent of the peripheral immune system and identify potential glia-specific targets for therapeutic intervention.

2024-08-26 | GSE238221 | GEO

Altered oligodendrocyte heterogeneity in Multiple sclerosis.

Project description:Oligodendrocyte (OL) pathology is increasingly implicated in neurodegenerative diseases, as they are involved in metabolic support of axons and functional cross-talk with other brain cells. Rodent OLs are heterogeneous, with developmental and biological differences, but the extent of heterogeneity in the normal human brain and its contribution to any changes of disease remains unknown. Here we performed single nuclei RNA-sequencing (snRNA-seq) from white matter (WM) areas of post mortem human brain both in control (Ctr) and multiple sclerosis (MS) patients. We identified several sub-clusters of oligodendroglia in the Ctr human WM, some similar to those in mouse, and defined new markers for these. Strikingly, some of these sub-clusters were under-represented in MS tissue, while others were more prevalent than in controls. There was a lack of OL precursor cells (OPCs) and OLs in an intermediate stage of differentiation in MS lesions and in normal appearing white matter (NAWM), suggesting either depletion by the disease or by a regenerative response. The differences in mature OL sub-clusters indicate different functional states of OLs in MS tissue and, as this is similar in NAWM to lesions, that MS is a more diffuse brain disease than the focal demyelinating lesions suggest. We were also able to identify new markers of different MS lesion subtypes. Our findings of an altered heterogeneity of oligodendroglia in MS may have an important contribution to our understanding of disease progression and may alter therapeutic approaches to MS.

2019-01-23 | GSE118257 | GEO

Multiple sclerosis patient-derived CSF induces transcriptional changes in proliferating oligodendrocyte progenitors

Project description:This study provides an overview of the transcriptional signature of oligodendrocyte progenitor cells (OPCs) exposed to the CSF collected from multiple sclerosis patients with either a relapsing remitting disease course (RRMS) or a confirmed primary progressive diagnosis (PPMS). Using an Affymetrix microarray we were able to detect a set of common and unique genes for each treatment group. Gene ontology analysis revealed a common group of genes involved in protein transport, actin dynamics and response to stress and DNA damage, while the RRMS-specific genes were grouped according to protein complex biogenesis, nuclear transport and RNA processing. The transcriptional signature of progenitors exposed to PPMS was characterized by an up-regulation of the pro-differentiation adhesion molecule Lgals3. We confirmed increased protein levels of its gene product,product; galectin-3 in proliferating OPCs incubated with CSF from PPMS patients and also found a four-fold increase in mRNA transcript levels of galectin-3 in human post-mortem normal-appearing white matter samples of primary progressive MS patients when compared to non-neurological controls. This study will help to better understand the common and specific transcriptional changes induced in the different subtypes of MS and therefore find more specific molecular targets for each disease subtype. Comparison of transcriptional signature by microarray analysis of OPCs treated with RRMS and PPMS CSF.

2015-06-19 | E-GEOD-60881 | biostudies-arrayexpress

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