Graduate Students Korea University College of Medicine, Republic of Korea
Abstract: Neural organoids have been successfully used for modeling brain functions, studying neurodevelopmental disorders, and advancing drug development. However, traditional models often focus on limited brain regions, failing to capture the effects of entire brain regions. This can be particularly problematic in disease modeling and toxicity studies, as it limits the understanding of broader pathological phenomena that may occur across multiple brain regions. To address this issue, we established a simple and scalable method to generate a Multi-regional Neural Organoid Panel (MrNO). MrNO was produced through a streamlined three-stage culture process (neural induction → neural patterning → neural maturation), incorporating different cocktails of patterning factors to achieve anteroposterior and dorsoventral axis-dependent production of multiple organoids simultaneously. MrNO demonstrated high batch-to-batch reproducibility, validated by both morphological and transcriptomic analyses. This approach can be expanded to optimize conditions to produce other regionally specified organoids. Furthermore, through large-scale production, we faithfully identified toxic substances that induce primary and secondary microcephaly, revealing region-specific differential toxic responses. This platform extends single-region models to multi-region systems, facilitating the study of various brain regions and enabling a more holistic evaluation of pathological phenomena in neurodevelopmental defect screening.
Funding Source: This study was supported by the Bio & Medical Technology Development Program of the NRF (RS-2023-00225239). This research was also supported by a grant of the Korea Dementia Research Project through the KUCRF (RS-2024-00467876).
