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Modeling early phenotypes of Parkinson’s disease by age-induced midbrain-striatum assembloids [scRNA-Seq]

ABSTRACT: Modeling early phenotypes of Parkinson’s disease by age-induced midbrain-striatum assembloids [scRNA-Seq]

PROVIDER: PRJNA1009018 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25755687_1.fastq.gz	Fastqsanger.gz
	SRR25755687_2.fastq.gz	Fastqsanger.gz
	SRR25755688_1.fastq.gz	Fastqsanger.gz
	SRR25755688_2.fastq.gz	Fastqsanger.gz
	SRR25755689_1.fastq.gz	Fastqsanger.gz

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Modeling early phenotypes of Parkinson’s disease by age-induced midbrain-striatum assembloids [scRNA-Seq]

Project description:Parkinson’s disease, an aging-associated neurodegenerative disorder, is characterised by nigrostriatal pathway dysfunction caused by the gradual loss of dopaminergic neurons in the substantia nigra pars compacta of the midbrain. Human in vitro models are enabling the study of the dopaminergic neurons’ loss, but not the dysregulation within the dopaminergic network in the nigrostriatal pathway. Additionally, these models do not incorporate aging characteristics which potentially contribute to the development of Parkinson’s disease. Here we present a nigrostriatal pathway model based on midbrain-striatum assembloids with inducible aging. We show that these assembloids can develop characteristics of the nigrostriatal connectivity, with catecholamine release from the midbrain to the striatum and synapse formation between midbrain and striatal neurons. Moreover, Progerin-overexpressing assembloids acquire aging traits that lead to early neurodegenerative phenotypes. This model shall help to reveal the contribution of aging as well as nigrostriatal connectivity to the onset and progression of Parkinson’s disease.

2023-10-28 | GSE241631 | GEO

Modeling early phenotypes of Parkinson’s disease by age-induced midbrain-striatum assembloids [RNA-Seq]

2023-10-28 | GSE236458 | GEO

Modeling early phenotypes of Parkinson’s disease by age-induced midbrain-striatum assembloids

Project description:Modeling early phenotypes of Parkinson’s disease by age-induced midbrain-striatum assembloids

| PRJNA1009011 | ENA

Modeling early phenotypes of Parkinson’s disease by age-induced midbrain-striatum assembloids [RNA-Seq]

Project description:Modeling early phenotypes of Parkinson’s disease by age-induced midbrain-striatum assembloids [RNA-Seq]

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In vitro Modeling of the Human Dopaminergic System using spatially arranged ventral Midbrain-Striatum-Cortex Assembloids [Smartseq]

Project description:Dopaminergic neurons located in the ventral Midbrain (vMid) innervate the striatum and cortex and are involved in movement control and reward-related cognition. Degeneration of dopaminergic neurons causes Parkinson’s disease (PD), while their over-activation is implicated in addiction. Thus, modeling the dopaminergic system is of broad relevance for disease research and drug discovery, although limited availability of patient material and inherent differences in animal model systems are restricting the study of distinctive human specific features such as development and neurodegeneration. Here, we show that spatially arranged assembloids can recapitulate dopaminergic innervation of striatum and cortex and offer methods for their use in cell replacement therapy and addiction research. We describe improved protocols for growing vMid, striatal and cortical organoids and use custom embedding molds to fuse them in a linear manner. Linear assembloids form functional long-range dopaminergic connections with striatal and cortical tissues that can release dopamine. We demonstrate that vMid grafts derived from hPSCs for cell replacement therapy of PD can integrate into the tissue and structurally mature. Additionally, we demonstrate that our model can be used to study dopaminergic circuit perturbations in the example of chronic cocaine treatment which causes morphological, functional and transcriptional changes that remained altered even after drug withdrawal. Our method opens new avenues for dopaminergic cell replacement therapy and the analysis of drugs affecting the dopaminergic system, directly in a human system.

2023-09-20 | GSE219246 | GEO

In vitro Modeling of the Human Dopaminergic System using spatially arranged ventral Midbrain-Striatum-Cortex Assembloids [scRNAseq]

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In vitro Modeling of the Human Dopaminergic System using spatially arranged ventral Midbrain-Striatum-Cortex Assembloids

Project description:In vitro Modeling of the Human Dopaminergic System using spatially arranged ventral Midbrain-Striatum-Cortex Assembloids

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In vitro Modeling of the Human Dopaminergic System using spatially arranged ventral Midbrain-Striatum-Cortex Assembloids [Smartseq]

Project description:In vitro Modeling of the Human Dopaminergic System using spatially arranged ventral Midbrain-Striatum-Cortex Assembloids [Smartseq]

| PRJNA907800 | ENA

In vitro Modeling of the Human Dopaminergic System using spatially arranged ventral Midbrain-Striatum-Cortex Assembloids [scRNAseq]

Project description:In vitro Modeling of the Human Dopaminergic System using spatially arranged ventral Midbrain-Striatum-Cortex Assembloids [scRNAseq]

| PRJNA907801 | ENA

Modelling G2019S-LRRK2 sporadic Parkinson’s disease in 3D midbrain organoids

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.

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