ArticleProceedings of the National Academy of Sciences of the United States of America2024
Construction of human 3D striato-nigral assembloids to recapitulate medium spiny neuronal projection defects in Huntington's disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Mapping the Cerebral Organoid Landscape: A Systematic Review of Preclinical 3D Models in Neuroscience.Advanced healthcare materials · 2026Pooled it
- Organoids: Key advances, optimization, and technological iterations in their application to neurodegenerative diseases.Neural regeneration research · 2026Article
- Tutorial: interrogating biology using organoid technologies.Nature protocols · 2026Review
- Huntington's disease human lateral ganglionic eminence precursors differentiate into functionally mature medium spiny neurons exhibiting pathology.Stem cells (Dayton, Ohio) · 2026Article
- Advances and applications of brain organoids in central nervous system disorders: Bridging the gap from laboratory to clinic.Neural regeneration research · 2026Article
- Organoids - the future of pre-clinical development of AAV gene therapy for CNS disorders.Gene therapy · 2026Review
- Spinal cord extracellular matrix hydrogel enhances organoid maturation and functional regeneration after spinal cord injury.Materials today. Bio · 2026Article
- Insights into neurodevelopmental features of Huntington's disease from stem cell-derived models including organoids.Journal of Huntington's disease · 2026Review
- SHMT2 deficiency disrupts transcriptional regulation through homocysteine-mediated suppression of histone lactylation in Huntington's disease models.The Journal of clinical investigation · 2026Article
- Organizers in a dish: Modeling human CNS morphogenesis.Developmental cell · 2026Review
- Parabiosis, Assembloids, Organoids (PAO).Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Recreating the human brain: Are assembloids merely descriptive models?Frontiers in cellular neuroscience · 2026Review
- Towards learning and memory risk assessment with human brain organoids: barriers and opportunities.Frontiers in toxicology · 2026Review
- 3D cultured human medium spiny neurons functionally integrate and rescue motor deficits in Huntington's disease mice.The Journal of clinical investigation · 2025Article
- Article
- Brain organoid models of Huntington's disease shift the focus towards neurodevelopment.Disease models & mechanisms · 2025Article
- Advances, challenges, and opportunities of human midbrain organoids for modelling of the dopaminergic system.The EMBO journal · 2025Review
- Human Midbrain Organoids Enriched With Dopaminergic Neurons for Long-Term Functional Evaluation.Cell proliferation · 2025Article
- Brain organoids: building higher-order complexity and neural circuitry models.Trends in biotechnology · 2025Review
- Review
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16 authors.
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Abstract
The striato-nigral (Str-SN) circuit is composed of medium spiny neuronal projections that are mainly sent from the striatum to the midbrain substantial nigra (SN), which is essential for regulating motor behaviors. Dysfunction of the Str-SN circuitry may cause a series of motor disabilities that are associated with neurodegenerative disorders, such as Huntington's disease (HD). Although the etiology of HD is known as abnormally expanded CAG repeats of the huntingtin gene, treatment of HD remains tremendously challenging. One possible reason is the lack of effective HD model that resembles Str-SN circuitry deficits for pharmacological studies. Here, we first differentiated striatum-like organoids from human pluripotent stem cells (hPSCs), containing functional medium spiny neurons (MSNs). We then generated 3D Str-SN assembloids by assembling striatum-like organoids with midbrain SN-like organoids. With AAV-hSYN-GFP-mediated viral tracing, extensive MSN projections from the striatum to the SN are established, which formed synaptic connection with GABAergic neurons in SN organoids and showed the optically evoked inhibitory postsynaptic currents and electronic field potentials by labeling the striatum-like organoids with optogenetic virus. Furthermore, these Str-SN assembloids exhibited enhanced calcium activity compared to that of individual striatal organoids. Importantly, we further demonstrated the reciprocal projection defects in HD iPSC-derived assembloids, which could be ameliorated by treatment of brain-derived neurotrophic factor. Taken together, these findings suggest that Str-SN assembloids could be used for identifying MSN projection defects and could be applied as potential drug test platforms for HD.
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