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A Scalable Micropatterned Organoid Platform for Quantitative Modeling of Human Forebrain Development and Disease

ABSTRACT: Brain organoids derived from human pluripotent stem cells have revolutionized the modeling of neurodevelopment and associated disorders. However, challenges of morphological variability and limited scalability restrict their use for high-throughput disease phenotyping and drug-screens. Here, we introduce a micropatterned organoid platform enabling reproducible and scalable generation of forebrain-like structures. By integrating micropatterning with established cortical differentiation protocols, we generate reproducible, miniaturized brain organoids that are suitable for AI-based, quantitative phenotypic analysis. As a proof-of-concept, we model DYRK1A syndrome, a neurodevelopmental disorder characterized by microcephaly and autism spectrum disorder, using genetically engineered isogenic embryonic stem cells (hESCs) and patient-derived induced pluripotent stem cells (iPSCs). Multi-omics and high-content imaging reveal that DYRK1A haploinsufficiency disrupts progenitor proliferation, delays neuronal differentiation, and impairs cortical organization. Our platform provides an efficient tool for early disease detection and analysis, and opens avenues toward phenotypic, genetic and pharmacological screens.

ORGANISM(S): Homo sapiens

PROVIDER: GSE293573 | GEO | 2026/06/01

REPOSITORIES: GEO

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