Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

SNP data from genomic DNA from a subject, fibroblasts, iPSCs and neurons with four copies of SNCA, and genomic DNA from an unaffected first degree relative and equivalent cell lines

ABSTRACT: A major barrier to research on Parkinson’s disease (PD) is inaccessibility of diseased tissue for study. One solution is to derive induced pluripotent stem cells (iPSCs) from patients with PD and differentiate them into neurons affected by disease. We created an iPSC model of PD caused by triplication of SNCA encoding α-synuclein. α-Synuclein dysfunction is common to all forms of PD, and SNCA triplication leads to fully penetrant familial PD with accelerated pathogenesis. After differentiation of iPSCs into neurons enriched for midbrain dopaminergic subtypes, those from the patient contain double α-synuclein protein compared to those from an unaffected relative, precisely recapitulating the cause of PD in these individuals. A measurable biomarker makes this model ideal for drug screening for compounds that reduce levels of α-synuclein, and for mechanistic experiments to study PD pathogenesis. This SNP microarray study was carried out to confirm presence of SNCA triplication in the affected subject and the derived cell lines.

ORGANISM(S): Homo sapiens

PROVIDER: GSE28366 | GEO | 2011/09/15

SECONDARY ACCESSION(S): PRJNA143169

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

SNP data from genomic DNA from a subject, fibroblasts, iPSCs and neurons with four copies of SNCA, and genomic DNA from an unaffected first degree relative and equivalent cell lines

Project description:A major barrier to research on Parkinson’s disease (PD) is inaccessibility of diseased tissue for study. One solution is to derive induced pluripotent stem cells (iPSCs) from patients with PD and differentiate them into neurons affected by disease. We created an iPSC model of PD caused by triplication of SNCA encoding ?-synuclein. ?-Synuclein dysfunction is common to all forms of PD, and SNCA triplication leads to fully penetrant familial PD with accelerated pathogenesis. After differentiation of iPSCs into neurons enriched for midbrain dopaminergic subtypes, those from the patient contain double ?-synuclein protein compared to those from an unaffected relative, precisely recapitulating the cause of PD in these individuals. A measurable biomarker makes this model ideal for drug screening for compounds that reduce levels of ?-synuclein, and for mechanistic experiments to study PD pathogenesis. This SNP microarray study was carried out to confirm presence of SNCA triplication in the affected subject and the derived cell lines. 11 samples were analysed: genomic DNA from the two subjects in the study, the two parent fibroblast lines (AST denoting alpha-synuclein triplication and NAS denoting normal alpha-synuclein), two iPSC lines from each parent fibroblast line (four in total), a human embryonic stem cell line (SHEF4) and two neuronal samples one each from AST and NAS iPSCs).

2011-09-14 | E-GEOD-28366 | biostudies-arrayexpress

Expression data from Parkison's iPSCs with four copies of SNCA, and equivalent cell lines from an unaffected first degree relative

Project description:A major barrier to research on Parkinson’s disease (PD) is inaccessibility of diseased tissue for study. One solution is to derive induced pluripotent stem cells (iPSCs) from patients with PD and differentiate them into neurons affected by disease. We created an iPSC model of PD caused by triplication of SNCA encoding α-synuclein. α-Synuclein dysfunction is common to all forms of PD, and SNCA triplication leads to fully penetrant familial PD with accelerated pathogenesis. After differentiation of iPSCs into neurons enriched for midbrain dopaminergic subtypes, those from the patient contain double α-synuclein protein compared to those from an unaffected relative, precisely recapitulating the cause of PD in these individuals. A measurable biomarker makes this model ideal for drug screening for compounds that reduce levels of α-synuclein, and for mechanistic experiments to study PD pathogenesis. This gene expression microarray study was carried out as part of the validation process for demonstrating that the generated iPSC lines are pluripotent. 5 samples were analysed: two clonal iPSC lines from each of two genotypes (four in total; AST denoting alpha-synuclein triplication and NAS denoting normal alpha-synuclein), a human embryonic stem cell line (SHEF4). All cultured in self-renewal conditions, mTeSR1

2011-09-14 | E-GEOD-30792 | biostudies-arrayexpress

Expression data from fibroblasts, iPSCs and neurons with four copies of SNCA, and equivalent cell lines from an unaffected first degree relative

Project description:A major barrier to research on Parkinson’s disease (PD) is inaccessibility of diseased tissue for study. One solution is to derive induced pluripotent stem cells (iPSCs) from patients with PD and differentiate them into neurons affected by disease. We created an iPSC model of PD caused by triplication of SNCA encoding α-synuclein. α-Synuclein dysfunction is common to all forms of PD, and SNCA triplication leads to fully penetrant familial PD with accelerated pathogenesis. After differentiation of iPSCs into neurons enriched for midbrain dopaminergic subtypes, those from the patient contain double α-synuclein protein compared to those from an unaffected relative, precisely recapitulating the cause of PD in these individuals. A measurable biomarker makes this model ideal for drug screening for compounds that reduce levels of α-synuclein, and for mechanistic experiments to study PD pathogenesis. This gene expression microarray study was carried out as part of the validation process for demonstrating that the generated iPSC lines are pluripotent. 15 samples were analysed: the two parent fibroblast lines (AST denoting alpha-synuclein triplication and NAS denoting normal alpha-synuclein), two iPSC lines from each parent fibroblast line (four in total), a human embryonic stem cell line (SHEF4) and eight neuronal samples (each iPSC line differentiated into a neuronal population enriched for dopaminergic neurons, at two different time points).

2011-09-14 | E-GEOD-28365 | biostudies-arrayexpress

Expression data from Parkinson's iPSCs with four copies of SNCA, and equivalent cell lines from an unaffected first degree relative

Project description:A major barrier to research on Parkinson’s disease (PD) is inaccessibility of diseased tissue for study. One solution is to derive induced pluripotent stem cells (iPSCs) from patients with PD and differentiate them into neurons affected by disease. We created an iPSC model of PD caused by triplication of SNCA encoding α-synuclein. α-Synuclein dysfunction is common to all forms of PD, and SNCA triplication leads to fully penetrant familial PD with accelerated pathogenesis. After differentiation of iPSCs into neurons enriched for midbrain dopaminergic subtypes, those from the patient contain double α-synuclein protein compared to those from an unaffected relative, precisely recapitulating the cause of PD in these individuals. A measurable biomarker makes this model ideal for drug screening for compounds that reduce levels of α-synuclein, and for mechanistic experiments to study PD pathogenesis. This gene expression microarray study was carried out as part of the validation process for demonstrating that the generated iPSC lines are pluripotent.

2011-09-15 | GSE30792 | GEO

Expression data from fibroblasts, iPSCs and neurons with four copies of SNCA, and equivalent cell lines from an unaffected first degree relative

Project description:A major barrier to research on Parkinson’s disease (PD) is inaccessibility of diseased tissue for study. One solution is to derive induced pluripotent stem cells (iPSCs) from patients with PD and differentiate them into neurons affected by disease. We created an iPSC model of PD caused by triplication of SNCA encoding α-synuclein. α-Synuclein dysfunction is common to all forms of PD, and SNCA triplication leads to fully penetrant familial PD with accelerated pathogenesis. After differentiation of iPSCs into neurons enriched for midbrain dopaminergic subtypes, those from the patient contain double α-synuclein protein compared to those from an unaffected relative, precisely recapitulating the cause of PD in these individuals. A measurable biomarker makes this model ideal for drug screening for compounds that reduce levels of α-synuclein, and for mechanistic experiments to study PD pathogenesis. This gene expression microarray study was carried out as part of the validation process for demonstrating that the generated iPSC lines are pluripotent.

2011-09-15 | GSE28365 | GEO

RNA-seq of human midbrain organoid models of Parkinson's Disease

Project description:Parkinson’s disease (PD) is a prevalent neurodegenerative disorder that is characterized by the selective loss of midbrain dopamine (DA)-producing neurons and the formation of α-synuclein (α-syn)-containing inclusions named Lewy bodies (LBs). Here, we report that the loss of glucocerebrosidase (GCase), coupled with α-syn overexpression, result in substantial accumulation of detergent-resistant α-syn aggregates and Lewy body-like inclusions (LBLIs) in human midbrain-like organoids (hMLOs). These LBLIs exhibit a highly similar structure to PD-associated LBs, by displaying a spherically symmetric morphology with an eosinophilic core, and containing α-syn and ubiquitin. Importantly, hMLOs generated from PD patient-derived inducible pluripotent stem cells (iPSCs) harboring SNCA triplication also exhibit subsequent degeneration of DA neurons and LBLI formation upon chronic GCase inhibitor treatment. Taken together, our hMLOs harbouring two major PD risk factors (GCase deficiency and overproduced α-syn) successfully recapitulate major pathophysiological signatures of the disease, and highlight the broad utility of brain organoid technology in modeling human neurodegenerative diseases.

2021-08-13 | E-MTAB-7302 | biostudies-arrayexpress

Expression and SNP data from fibroblasts, iPSCs and neurons with four copies of SNCA, and equivalent cell lines from an unaffected first degree relative

Project description:This SuperSeries is composed of the following subset Series: GSE28365: Expression data from fibroblasts, iPSCs and neurons with four copies of SNCA, and equivalent cell lines from an unaffected first degree relative GSE28366: SNP data from genomic DNA from a subject, fibroblasts, iPSCs and neurons with four copies of SNCA, and genomic DNA from an unaffected first degree relative and equivalent cell lines Refer to individual Series from fibroblasts, iPSCs and neurons with four copies of SNCA, and equivalent cell lines from an unaffected first degree relative

2011-09-14 | E-GEOD-28367 | biostudies-arrayexpress

Single cell RNA sequencing data of SNCA triplication cortical organoids

Project description:Aggregated α-synuclein (α-SYN) proteins, encoded by the SNCA gene, are hallmarks of Lewy body disease (LBD), affecting multiple brain regions. However, the specific mechanisms underlying α-SYN pathology in cortical neurons, crucial for LBD-associated dementia, remain unclear. Here, we generated human cortical LBD models by differentiating induced pluripotent stem cells (iPSCs) from SNCA triplication LBD patients into cerebral organoids and observed increased levels of pathological α-SYN in these organoids. Single-cell RNA sequencing revealed prominent expression of the SNCA gene in excitatory neurons, which exhibited synaptic and mitochondrial dysfunction, consistent with findings in the cortex of LBD human brains. Furthermore, screening 1280 FDA-approved drugs identified four candidates, which inhibited α-SYN seeding in RT-QuIC assay, reduced α-SYN aggregation and alleviated mitochondrial dysfunction in SNCA triplication iPSC models. Our findings provide valuable insights into the development of cortical LBD models and the discovery of potential drugs targeting α-SYN aggregation.

2024-09-18 | GSE236002 | GEO

Single nucleus RNA sequencing data of Lewy Body Dementia (LBD) brains

2024-09-18 | GSE235914 | GEO

Single cell RNA sequencing analysis of midbrain organoids with SNCA gene triplication modeling key features of synuclienopathy

Project description:SNCA, the first gene associated with Parkinson’s disease, encodes the α-synuclein protein, the predominant component within pathological inclusions termed Lewy bodies. We use 3D midbrain organoids, differentiated from human induced pluripotent stem cells derived from patients carrying a triplication of the SNCA gene and from CRISPR/Cas9 corrected isogenic control iPSCs. These human midbrain organoids recapitulate key features of α-synuclein pathology observed in the brains of patients with synucleinopathies. We used single cell RNA sequencing to characterize the cell types within these organoids. We find an equal proportion of neuronal and glial cells. The neuronal populations consist of dopmainergic, excitatory and inhibitory neurons in early and late stages of maturation as well as neural precursor cells. The glial populations consist of dividing radial glia, radial glia, astrocytes and early oligodendorcytes.

2021-11-02 | GSE186780 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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