ArticleStem cell reports2021
Pluripotent stem cell derived dopaminergic subpopulations model the selective neuron degeneration in Parkinson's disease.
Article in Stem cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 33 citations in OpenAlex.
- Engineering functional ventral midbrain dopaminergic neurons in human organoids through WNT modulation and bioreactor culture.Molecular psychiatry · 2026Article
- Individualized Bayesian Inference Identifies Novel Genetic Variants for Parkinson's Disease.Genetic epidemiology · 2026Article
- VMAT2 dysfunction impairs vesicular dopamine uptake, driving its oxidation and α-synuclein pathology in DJ-1-linked Parkinson's neurons.Science advances · 2026Article
- Organizers in a dish: Modeling human CNS morphogenesis.Developmental cell · 2026Review
- Stem cells strike back: advancements in Alzheimer's and Parkinson's disease treatment and modeling efforts from 2019 to 2024.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Transgenic iPSC Lines with Genetically Encoded MitoTimer to Study Mitochondrial Biogenesis in Dopaminergic Neurons with Tauopathy.Biomedicines · 2025Article
- Sox6 and ALDH1A1 Truncation by Asparagine Endopeptidase Defines Selective Neuronal Vulnerability in Parkinson's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Selective dopaminergic neurotoxicity modulated by inherent cell-type specific neurobiology.Neurotoxicology · 2024Review
- Detection of ER Stress in iPSC-Derived Neurons Carrying the p.N370S Mutation in theBiomedicines · 2024Article
- Comparative study of enriched dopaminergic neurons from siblings with Gaucher disease discordant for parkinsonism.bioRxiv : the preprint server for biology · 2024Article
- Expression and role of nicotinic acetylcholine receptors during midbrain dopaminergic neuron differentiation from human induced pluripotent stem cells.Neuropsychopharmacology reports · 2023Article
- Overexpression of Parkin in the Neuronal Progenitor Cells from a Patient with Parkinson's Disease Shifts the Transcriptome Towards the Normal State.Molecular neurobiology · 2023Article
- Early Differentiation Signatures in Human Induced Pluripotent Stem Cells Determined by Non-Targeted Metabolomics Analysis.Metabolites · 2023Article
- Defining the unknowns for cell therapies in Parkinson's disease.Disease models & mechanisms · 2022Article
- Single-cell transcriptomics reveals the cell fate transitions of human dopaminergic progenitors derived from hESCs.Stem cell research & therapy · 2022Article
- An efficient simplified method for the generation of corneal epithelial cells from human pluripotent stem cells.Human cell · 2022Article
- Parkinson's disease in the single-cell era.Nature neuroscience · 2022Article
- Neuroprotection and Disease Modification by Astrocytes and Microglia in Parkinson Disease.Antioxidants (Basel, Switzerland) · 2022Review
- Generation of aCells · 2022Article
- Evidence That Substantia Nigra Pars Compacta Dopaminergic Neurons Are Selectively Vulnerable to Oxidative Stress Because They Are Highly Metabolically Active.Frontiers in cellular neuroscience · 2022Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
Abstract
In Parkinson's disease (PD), substantia nigra (SN) dopaminergic (DA) neurons degenerate, while related ventral tegmental area (VTA) DA neurons remain relatively unaffected. Here, we present a methodology that directs the differentiation of mouse and human pluripotent stem cells toward either SN- or VTA-like DA lineage and models their distinct vulnerabilities. We show that the level of WNT activity is critical for the induction of the SN- and VTA-lineage transcription factors Sox6 and Otx2, respectively. Both WNT signaling modulation and forced expression of these transcription factors can drive DA neurons toward the SN- or VTA-like fate. Importantly, the SN-like lineage enriched DA cultures recapitulate the selective sensitivity to mitochondrial toxins as observed in PD, while VTA-like neuron-enriched cultures are more resistant. Furthermore, a proteomics approach led to the identification of compounds that alter SN neuronal survival, demonstrating the utility of our strategy for disease modeling and drug discovery.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.