ArticleThe Journal of clinical investigation2022
Human midbrain dopaminergic neuronal differentiation markers predict cell therapy outcomes in a Parkinson's disease model.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 49 citations in OpenAlex.
- Article
- Beyond phenotypic markers: rethinking dopaminergic identity in iPSC-derived neurons.Cell communication and signaling : CCS · 2026Review
- Impaired NADH-linked mitochondrial respiration disrupts ventral midbrain neuronal programs in POLG disease.Journal of translational medicine · 2026Article
- Cryopreservable dopaminergic progenitors derived from human iPSCs with accelerated loss of pluripotency and early functional restoration in Parkinsonian rats.NPJ Parkinson's disease · 2026Article
- Modulation of WNT and FGF18 enhances yield and subtype identity of hPSC-derived midbrain dopamine neurons.The Journal of clinical investigation · 2026Article
- Human pluripotent stem cell engineering with CRISPR-Cas9 for Parkinson's disease.Experimental & molecular medicine · 2026Review
- Distinct radial glia subtypes regulate midbrain dopaminergic neuron development.Nature neuroscience · 2026Article
- Long-read whole-genome sequencing of SHR rat substrains with distinct substance use phenotypes.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Article
- In vitro derivation of midbrain dopaminergic neurons from porcine embryonic stem cells in multi-dimensional conditions.Stem cell research & therapy · 2025Article
- BrainSTEM: A single-cell multiresolution fetal brain atlas reveals transcriptomic fidelity of human midbrain cultures.Science advances · 2025Article
- Review
- Engineering Cell Fate with Adaptive Feedback Control.ACS synthetic biology · 2025Article
- BMP, MEK, and WNT inhibition with NGN2 expression for rapid generation of hiPSC-derived neurons amenable to regional patterning.Stem cell reports · 2025Article
- Stem cell therapy for Parkinson's disease: A new hope for neural regeneration.World journal of biological chemistry · 2025Review
- Regenerating Locus Coeruleus-Norepinephrine (LC-NE) Function: A Novel Approach for Neurodegenerative Diseases.Cell proliferation · 2025Review
- Patterning effects of FGF17 and cAMP on generation of dopaminergic progenitors for cell replacement therapy in Parkinson's disease.Stem cells (Dayton, Ohio) · 2025Article
- Review
- Remodeling of Mitochondria-Endoplasmic Reticulum Contact Sites Accompanies LUHMES Differentiation.Biomolecules · 2025Article
- Integrative multiomics reveals common endotypes across PSEN1, PSEN2, and APP mutations in familial Alzheimer's disease.Alzheimer's research & therapy · 2025Article
- The Programme for Manufacture of hPSC‑Based Products for AMD and PD.Advances in experimental medicine and biology · 2025Review
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human pluripotent stem cell-based (hPSC-based) replacement therapy holds great promise for the treatment of Parkinson's disease (PD). However, the heterogeneity of hPSC-derived donor cells and the low yield of midbrain dopaminergic (mDA) neurons after transplantation hinder its broad clinical application. Here, we have characterized the single-cell molecular landscape during mDA neuron differentiation. We found that this process recapitulated the development of multiple but adjacent fetal brain regions including the ventral midbrain, the isthmus, and the ventral hindbrain, resulting in a heterogenous donor cell population. We reconstructed the differentiation trajectory of the mDA lineage and identified calsyntenin 2 (CLSTN2) and protein tyrosine phosphatase receptor type O (PTPRO) as specific surface markers of mDA progenitors, which were predictive of mDA neuron differentiation and could facilitate high enrichment of mDA neurons (up to 80%) following progenitor cell sorting and transplantation. Marker-sorted progenitors exhibited higher therapeutic potency in correcting motor deficits of PD mice. Different marker-sorted grafts had a strikingly consistent cellular composition, in which mDA neurons were enriched, while off-target neuron types were mostly depleted, suggesting stable graft outcomes. Our study provides a better understanding of cellular heterogeneity during mDA neuron differentiation and establishes a strategy to generate highly purified donor cells to achieve stable and predictable therapeutic outcomes, raising the prospect of hPSC-based PD cell replacement therapies.
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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.