Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RNA-seq analysis for mRNA expression change in alpha-synclein fibril-treated cultured oligodendrocyte precursor cells

ABSTRACT: Glial cytoplasmic inclusion is the pathological hallmark of multiple system atrophy commonly observed as alpha-synulcien-positive aggregates within oligodendrocytes. We elucidated that preformed alpha-synulcien fibrils triggers multimerization and upsurge of endogenous alpha-synulcien in oligodendrocyte precursor cells which is attributable to insufficient autophagic proteolysis. To assess the functional influence of alpha-synuclein fibrils application on oligodendrocyte precursor cells, RNA-seq analysis was performed. The data revealed that alpha-synulcien fibrils interfered with numerous protein expressions associated with neuronal support and myelination.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE107582 | GEO | 2017/12/02

SECONDARY ACCESSION(S): PRJNA420725

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Neurodegeneration and Neuroinflammation are Linked, but Independent of α-Synuclein Inclusions, in a Seeding/Spreading Mouse Model of Parkinson’s Disease

Project description:A key process of neurodegeneration in Parkinson's disease (PD) is the transneuronal spreading of alpha-synuclein. Alpha-synuclein is a presynaptic protein that is implicated in the pathogenesis of PD and other synucleinopathies, where it forms, upon intracellular aggregation, pathological inclusions. Other hallmarks of PD include neurodegeneration and microgliosis in susceptible brain regions. Whether it is primarily transneuronal spreading of a-synuclein particles, inclusion formation, or other mechanisms, such as inflammation, that cause neurodegeneration in PD is unclear. We used spreading/aggregation of alpha-synuclein induced by intracerebral injection of a-synuclein preformed fibrils into the mouse brain to address this question. We performed quantitative histological analysis for a-synuclein inclusions, neurodegeneration, and microgliosis in different brain regions, and a gene expression profiling of the ventral midbrain, at two different timepoints after disease induction. We observed significant neurodegeneration and microgliosis in brain regions not only with, but also withouta-synuclein inclusions. We also observed prominent microgliosis in injured brain regions that did not correlate with neurodegeneration nor with inclusion load. In longitudinal gene expression profiling experiments, we observed early and unique alterations linked to microglial mediated inflammation that preceded neurodegeneration, indicating an active role of microglia in inducing neurodegeneration. Our observations indicate that a-synuclein inclusion formation is not the major driver in the early phases of PD-like neurodegeneration, but that diffusible, oligomeric a-synuclein species, which induce unusual microglial reactivity, play a key role in this process.

2020-11-02 | GSE155716 | GEO

Phenotypic manifestation of alpha-synuclein strains from Parkinson’s disease and multiple system atrophy in human dopaminergic neruons

Project description:Although α-synucleinis implicated in the pathogenesis of Parkinson’s disease and related disorders, it remains unclear whether specific conformations or levels of α-synuclein assemblies are toxic and how they cause progressive loss of human dopaminergic neurons. To address this issue, we used iPSC-derived dopaminergic neurons with a-synuclein triplication or controls where endogenous α-synuclein was imprinted into synthetic or disease-relevant conformations. We used α-synuclein fibrils generated de novo or amplified from homogenates of brains affected with Parkinson’s disease (n=3) .We found that a 2.5-fold increase in α-synuclein levels in α-synuclein gene triplication neurons promoted seeded aggregation in a dose and time-dependent fashion, which was associated with a further increase in α-synuclein gene expression.Transcriptomic analysis and isogenic correction of α-synuclein triplication revealed that intraneuronal α-synuclein levels solely and sufficiently explained vulnerability to cell death.

2020-09-02 | GSE149632 | GEO

Oligodendrocyte-lineage cell-secreted L-type prostaglandin D synthase promotes oligodendrocyte differentiation and myelination

Project description:We used RNA sequencing to examine the transcriptional changes in differentiated oligodendrocytes, oligodendrocyte precursor cells, astroctytes, and microglia after blocking exocytosis from oligodendrocyte-lineage cells

2022-10-31 | GSE168569 | GEO

Quantitative proteome analyses of two types of Parkinson’s disease mouse model revealed potential pathways of the pathogenesis

Project description:Parkinson’s disease is the second most common neurodegenerative disorder that results in motor dysfunction and eventually cognitive impairment. -Synuclein protein has been known to be the most culprit protein but the clear pathological mechanism remains to be elucidated. As an effort to clarify the pathogenesis mechanism by -synuclein, various Parkinson’s disease mouse models with -synuclein overexpression have been developed. However, the systemic analysis of protein abundance change by the overexpressed -synuclein in whole proteome level still has been lacking. To address this issue, we established two different types of Parkinson’s disease model mice by injecting preformed -synuclein fibrils or inducing the expression of A53T mutant -synuclein to discover overlapping pathway, which is altered in the two different types of Parkinson’s disease mouse models. For more accurate quantification of mouse brain proteome, stable isotope labeling with amino acid in mammal-based quantification was implemented. As a result, we have successfully identified a total of 8,355 proteins from both of the mouse models; ~6,800 and ~7,200 proteins from preformed -synuclein fibrils injected model and A53T mutant -synuclein over-expressing model, respectively. From the pathway analysis of the differentially expressed proteins in common, complement and coagulation cascade pathway was recognized as the most enriched one. This is the first study that sheds light on the significance of the complement and coagulation pathway in the pathogenesis of PD through proteome analyses with two different types of Parkinson’s disease mouse models.

2021-06-05 | PXD015293 | Pride

Phenotypic manifestation of alpha-synuclein strains derived from Parkinson’s disease and multiple system atrophy in human dopaminergic neurons

Project description:Althougha-synuclein is implicated in the pathogenesis of Parkinson’s disease and related disorders, it remains unclear whether specific conformations or levels ofa-synuclein assemblies are toxic and how they cause progressive loss of human dopaminergic neurons. To address this issue, we used iPSC-derived dopaminergic neurons with a-synuclein triplication or controls where endogenous a-synuclein was imprinted into synthetic or disease-relevant conformations. We used a-synuclein fibrils generated de novo or amplified from homogenates of brains affected with Parkinson’s disease (n=3) or multiple system atrophy (n=5). We found that a 2.5-fold increase in a-synuclein levels in a-synuclein gene triplication neurons promoted seeded aggregation in a dose and time-dependent fashion, which was associated with a further increase in a-synuclein gene expression. Progressive neuronal loss was observed only in a-synuclein triplication neurons seeded with brain-amplified fibrils. Transcriptomic analysis and isogenic correction of a-synuclein triplication revealed that intraneuronalalpha-synuclein levels solely and sufficiently explained vulnerability to neuronal death

2021-04-13 | GSE171999 | GEO

Expression profiles in Chd7 knockdown oligodendrocyte precursor cells

Project description:Oligodendrocytes are generated from oligodendrocyte precursor cells (OPCs). Chd7 is ATP-dependent chromatin-remodeling enzyme. We performed microarray analysis to examine changes in gene expression between control and Chd7 knockdown OPCs. Results provide insight into the function of Chd7 in oligodendrocyte development.

2018-03-01 | GSE95347 | GEO

Investigation of Oligodendrocyte Precursor Cell Differentiation by Quantitative Proteomics

Project description:Oligodendrocytes, the myelinating cells of the central nervous system, are essential for correct brain function. They originate from oligodendrocyte precursor cells (OPCs) through a differentiation process which is only incompletely understood and impaired in a variety of demyelinating diseases. Better knowledge of this differentiation holds the promise to develop novel therapies for these disorders. We investigated the differentiation of rat oligodendrocyte precursor cells to oligodendrocytes in vitro. After confirmation of differentiation by immunohistochemical analysis using cell type-specific marker proteins, we conducted a quantitative proteomics study using tandem mass tags (TMT). We investigated four time points of differentiation covering early, intermediate, and late stages. Data analysis was perfomed using Mascot and Maxquant.

2019-06-21 | PXD012544 | Pride

Distinct microglia subsets are associated with α-synucleinopathy in multiple system atrophy

Project description:We developed a novel mice model of multiple system atrophy (MSA)-cerebellar type (MSA-C) by over-expression of human mutant α-synuclein (α-syn) in oligodendrocyte using Tet-off system. We identified distinct microglial subpopulations in a novel MSA-C model mice.

2022-09-06 | GSE209944 | GEO

Transcriptome analysis of LRRK2 knock-out microglia cells reveals T alterations of inflammatory- and oxidative stress-related pathways upon treatment with α-synuclein fibrils

Project description:We used the RNA-Sequencing to obtain transcriptomic profiles of LRRK2 wild-type (WT) and knock-out (KO) microglia cells treated with α-synuclein pre-formed fibrils (PFFs) or lipopolysaccharide (LPS) as a general inflammatory insult. Conclusion: overall, the results suggest that microglial LRRK2 may contribute to the pathogenesis of PD via altered oxidative stress signaling.

2021-10-26 | GSE186483 | GEO

Single-cell transcriptomic analysis of human and mouse oligodendrocyte precursor cells

Project description:We report single cell gene expression analysis of human fetal and mouse postnatal oligodendrocyte precursor cells

2023-09-13 | GSE214086 | GEO