Modeling PD in midbrain-like organoids
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA525884 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description: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.
2025-04-01 | GSE275820 | GEO
Project description:Progressive Supranuclear Palsy–Richardson Syndrome (PSP-RS) is a rare, rapidly progressive neurodegenerative tauopathy frequently misdiagnosed as Parkinson’s Disease (PD) due to overlapping clinical features. The lack of reliable molecular biomarkers for early and differential diagnosis presents a major clinical challenge. To address this, we developed human midbrain organoids from induced pluripotent stem cells (iPSCs) derived from patients with sporadic PSP-RS, PD, and healthy controls (HCs), and profiled microRNA (miRNA) expression dynamics using small RNA sequencing. These 3D organoid models faithfully recapitulate key pathological hallmarks, including tau hyperphosphorylation in PSP-RS and Lewy body–like α-synuclein inclusions in PD. Our analysis revealed temporally dynamic, disease-specific miRNA signatures: miR-5683, miR-873-5p, miR-219b-5p, and miR-219a-2- 3p were selectively upregulated in PSP-RS, whereas PD organoids showed increased levels of miR-1-3p, miR-133b, miR-10b-5p, and miR-199a-5p. Additionally, miR-5683, miR-3085- 3p, miR-138-2-3p, and miR-124-3p emerged as key discriminators between PSP-RS and HCs. These findings highlight the utility of iPSC-derived midbrain organoids as a translationally relevant platform to uncover disease-specific regulatory networks and identify candidate miRNA biomarkers for atypical parkinsonian syndromes.
2025-08-20 | GSE294029 | GEO
Project description:Recent advances in generating 3 dimensional (3D) organoid systems from stem cells offer new possibilities for disease modeling. In this study, we generate isogenic 3D midbrain organoids with or without a Parkinson’s disease-associated LRRK2 G2019S mutation. LRRK2-G2019S midbrain organoids derived from LRRK2 targeted human iPSCs in vitro have LRRK2-associated sporadic Parkinson's disease phenotypes. Midbrain-like 3D organoids expressing LRRK2-G2019S showed dynamic changes in globle gene expression.
2019-02-02 | GSE125234 | GEO
Project description:In this study, midbrain-like organoids were yielded from hPSCs to prepare cells used for PD therapy. Neural stem/precursor cells (NSCs) isolated from midbrain organoids (Og-NSCs) expanded stably and differentiated into mDA neurons, and an unprecedentedly high proportion express midbrain-specific factors.
2020-02-29 | GSE142505 | GEO
Project description:In this study, midbrain-like organoids were yielded from hPSCs to prepare cells suitable for PD therapy. Neural stem/precursor cells (NSCs) isolated from midbrain organoids (Og-NSCs) expanded stably and differentiated into mDA neurons, and an unprecedentedly high proportion express midbrain-specific factors.
2020-01-23 | GSE144062 | GEO
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
Project description:The mechanisms underlying Parkinson's disease (PD) etiology are only partially understood despite intensive research conducted in the field. Recent evidence suggests that early neurodevelopmental defects might play a role in cellular susceptibility to neurodegeneration. To study the early developmental contribution of GBA mutations in PD we used patient-derived iPSCs carrying a heterozygous N370S mutation in the GBA gene. Patient-specific midbrain organoids displayed GBA-PD relevant phenotypes such as reduction of GCase activity, autophagy impairment and mitochondrial dysfunction. Genome-scale metabolic (GEM) modeling predicted changes in lipid metabolism which were validated with lipidomics analysis, showing significant differences in the lipidome of GBA-PD. In addition, patient-specific midbrain organoids exhibited an increase in the neural progenitor population showing signs of cellular senescence. This was accompanied by a decrease in the number and complexity of dopaminergic neurons. These results provide insights into how GBA mutations may lead to neurodevelopmental defects thereby predisposing to PD pathology.
2022-07-24 | GSE208783 | GEO
Project description:The mechanisms underlying Parkinson's disease (PD) etiology are only partially understood despite intensive research conducted in the field. Recent evidence suggests that early neurodevelopmental defects might play a role in cellular susceptibility to neurodegeneration. To study the early developmental contribution of GBA mutations in PD we used patient-derived iPSCs carrying a heterozygous N370S mutation in the GBA gene. Patient-specific midbrain organoids displayed GBA-PD relevant phenotypes such as reduction of GCase activity, autophagy impairment and mitochondrial dysfunction. Genome-scale metabolic (GEM) modeling predicted changes in lipid metabolism which were validated with lipidomics analysis, showing significant differences in the lipidome of GBA-PD. In addition, patient-specific midbrain organoids exhibited an increase in the neural progenitor population showing signs of cellular senescence. This was accompanied by a decrease in the number and complexity of dopaminergic neurons. These results provide insights into how GBA mutations may lead to neurodevelopmental defects thereby predisposing to PD pathology.
2022-07-24 | GSE208781 | GEO
Project description:Recent advances in three dimensional (3D) culture systems have led to the generation of brain organoids that share resemblance to different parts of the human brains; however, a 3D organoid model of the midbrain that contains functional midbrain dopaminergic (mDA) neurons has not been reported. In this study, we develop a method to differentiate human PSCs into a large multicellular organoid-like structure that contains distinct layers of neuronal cells with a transcriptomic profile that resembles human prenatal midbrain. Importantly, we detected electrically active and functionally mature mDA neurons, and dopamine production in our 3D midbrain-like organoids (MLOs). In contrast to human mDA neurons generated using non-3D methods or in the MLOs generated from mouse embryonic stem cells, our human MLOs uniquely produced neuromelanin-like granules that were structurally similar to those isolated from human substantia nigra tissues. Thus our MLOs bearing features of the human midbrain may provide a novel tractable in vitro system to study the human midbrain and its related diseases.
2016-08-24 | E-MTAB-4868 | biostudies-arrayexpress
Project description:Midbrain organoids are advanced in vitro cellular models for disease modelling. They have been used successfully over the past decade for Parkinson’s disease (PD) research and drug development. The three-dimensional structure and multicellular composition allow disease research under more physiological conditions than is possible with conventional 2D cellular models. However, there are concerns in the field regarding the organoid batch-to-batch variability and thus the reproducibility of the results. In this manuscript, we generate multiple independent midbrain organoid batches derived from healthy individuals or GBA-N370S mutation-carrying PD patients to evaluate the reproducibility of the GBA-N370S mutation-associated PD transcriptomic and metabolic signature as well as selected protein abundance. Our analysis shows that GBA-PD-associated phenotypes are reproducible across organoid generation batches and time points. This proves that midbrain organoids are not only suitable for PD in vitro modelling, but also represent robust and highly reproducible cellular models.
2025-07-08 | GSE287566 | GEO