Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Gene expression profile of healthy control organoids, a Parkinson disease patient specific midbrain organoid carrying a triplication in the SNCA gene and two healthy control organoids co-cultured with either healthy or PD hindbrain organoids

ABSTRACT: Single nuclei RNAseq was used to characterize the cell diversity in healthy control hindbrain organoids, as well as in PD midbrain organoids. Sequencing of healthy midbrain organoids after co-culture with either healthy or PD hinbrain organoids was used to compare the influence of the healthy versus the disease hindbrain context to the healthy midbrain model.

ORGANISM(S): Homo sapiens

PROVIDER: GSE275820 | GEO | 2025/04/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Gene expression profile of healthy control organoids, a Parkinson disease patient specific midbrain organoid carrying a triplication in the SNCA gene and two healthy control organoids co-cultured with either healthy or PD hindbrain organoids

Project description:Gene expression profile of healthy control organoids, a Parkinson disease patient specific midbrain organoid carrying a triplication in the SNCA gene and two healthy control organoids co-cultured with either healthy or PD hindbrain organoids

| PRJNA1153030 | ENA

Synaptic decline precedes dopaminergic neuronal loss in human midbrain organoids harboring a triplication of the SNCA gene

Project description:Increased levels of the protein alpha-synuclein (α-syn) are associated with the development of neurodegenerative diseases like Parkinson's disease (PD). In physiological conditions, α-syn modulates synaptic plasticity, neurogenesis and neuronal survival. Here, we used a PD patient specific midbrain organoid model derived from induced pluripotent stem cells harboring a triplication in the SNCA gene to study PD-associated phenotypes. The model recapitulates the two main hallmarks of PD, which are α-syn aggregation and loss of dopaminergic neurons. Additionally, impairments in astrocyte differentiation were detected. Transcriptomics data indicate that synaptic function is impaired in PD specific midbrain organoids. This is further confirmed by alterations in synapse number and electrophysiological activity. We found that synaptic decline precedes neurodegeneration. Finally, this study substantiates that patient specific midbrain organoids allow a personalized phenotyping, which make them an interesting tool for precision medicine and drug discovery. However, its pathogenic accumulation and aggregation results in toxicity and neurodegeneration.

2024-12-02 | GSE278265 | GEO

SNCA triplication disrupts proteostasis and extracellular architecture prior to neurodegeneration in human midbrain organoids

Project description:Synucleinopathies, including Parkinsonâ€™s disease, are characterized by Î±-synuclein aggregation and progressive neurodegeneration, yet the early molecular events linking SNCA gene dosage to disrupted proteostasis remain poorly understood. Here, we used human midbrain organoids carrying an SNCA triplication (SNCA Trip) and the isogenic corrected line (SNCA Isog) to dissect early pathogenic mechanisms in a 3D human model of synucleinopathy. We combined immunohistochemistry, immunoblotting, tandem mass tag proteomics, bulk RNA sequencing, and ribosome profiling to systematically characterize molecular alterations in SNCA Trip organoids at day 50 (D50) and day 100 (D100) of maturation. SNCA Trip organoids exhibited increased Î±-synuclein accumulation, neuromelanin deposition, and activation of mTORC1 (p-rpS6), ERK1/2, and p-eIF2Î± signalling pathways by D100. Proteomic and transcriptomic analyses revealed upregulation of cytoskeletal, synaptic, and axonal development pathways, alongside significant downregulation of extracellular matrix (ECM) components. Ribosome profiling showed minimal global translational changes but uncovered selective translational buffering of neuronal and ECM-associated transcripts. Confocal imaging confirmed progressive disorganization of pericellular and interstitial ECM structures around neurons in SNCA Trip organoids. Our findings demonstrate that SNCA triplication induces early proteostatic disruption and extracellular matrix remodelling prior to neurodegeneration, suggesting that altered translation and ECM homeostasis may contribute to disease initiation and progression. Targeting these early aberrant mechanisms may offer new therapeutic opportunities for synucleinopathies, such as Parkinsonâ€™s Disease.

2026-04-06 | PXD063729 | Pride

Single cell profile of human iPSC-derived midbrain organoids from healthy individual, Parkinson disease patient harboring a Miro1R272Q mutation and its respective isogenic control

Project description:Midbrain organoids are 3D in vitro models, which represent the human midbrain and can be used as Parkinson's disease (PD) models. In the current study, we used single cell RNA sequencing (scRNA-seq) to investigate the effect of a novel mutation in the RhoT1 gene (Miro1 R272Q) in the PD pathology, and how it affect the dopaminergic neuron population present in the model.

2023-07-31 | GSE237133 | 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

Single cell RNA sequencing profile of 60 day old human iPSC-derived midbrain organoids from healthy individual, Parkinson’s disease patient (Miro1 p.R272Q mutation) and its isogenic control

Project description:Use of patient specific models, such as midbrain organoids, have shown to be valuable tools to models Parkinson’s disease as well as to identify novel pathological cellular and molecular mechanisms. In here, we used single cell RNA sequencing analysis of 60 day old midbrain organoids obtained from a Parkinson’s disease patient carrying the p.R272Q Miro1 mutation, its isogenic control and a healthy control to explore the effect of RhoT1 gene in different cellular populations present within the midbrain organoids (e.g. dopaminergic neurons, astrocytes) and the subsequent effect on the PD pathology.

2025-01-30 | GSE264097 | GEO

SNCA triplication disrupts proteostasis and extracellular architecture prior to neurodegeneration in human midbrain organoids [Ribo-seq]

Project description:Synucleinopathies, including Parkinson’s disease, are characterized by α-synuclein (SNCA) aggregation and progressive neurodegeneration, yet the early molecular events linking SNCA gene dosage to disrupted proteostasis remain poorly understood. Here, we used human midbrain organoids derived from induced pluripotent stem cells (iPSC) carrying an SNCA triplication (SNCA Trip) and the isogenic corrected line (SNCA Isog) to dissect early pathogenic mechanisms in a 3D human model of synucleinopathy. We combined immunohistochemistry, immunoblotting, tandem mass tag proteomics, bulk RNA sequencing, and ribosome profiling to systematically characterize molecular alterations in SNCA Trip organoids at day 50 (D50) and day 100 (D100) of maturation. SNCA Trip organoids exhibited increased α-synuclein accumulation, neuromelanin deposition, and activation of mTORC1 (p-rpS6), ERK1/2, AKT and p-eIF2α signalling pathways by D100. Proteomic and transcriptomic analyses revealed upregulation of cytoskeletal, synaptic, and axonal development pathways, alongside significant downregulation of extracellular matrix (ECM) components and upregulation of perineuronal net (PNN) genes. Ribosome profiling showed minimal global translational changes but uncovered selective translational buffering of neuronal and ECM-associated transcripts. Confocal imaging confirmed progressive disorganization of pericellular and interstitial ECM structures around neurons in SNCA Trip organoids. Our findings demonstrate that SNCA triplication induces early proteostatic disruption and extracellular matrix remodelling prior to neurodegeneration and suggest that altered gene expression and ECM homeostasis may contribute to disease initiation and progression. Targeting these early aberrant mechanisms may offer new therapeutic opportunities for synucleinopathies, such as Parkinson’s Disease.

2026-04-09 | GSE299914 | GEO

SNCA triplication disrupts proteostasis and extracellular architecture prior to neurodegeneration in human midbrain organoids [RNA-seq]

2026-04-09 | GSE299913 | GEO

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

Modeling PD in midbrain-like organoids

Project description:Modeling PD in midbrain-like organoids

| PRJNA525884 | ENA