Multiscale Comparative Analyses of OVB-Organoids and Cerebral Organoids

Organoid technology is critical for studying human brain development, but existing single-organoid culture systems fail to simulate inter-organ interactions (e.g., optic vesicle–brain) in embryogenesis. This study aimed to establish a more comprehensive in vitro model for early neurodevelopment. We established standardized protocols for cerebral organoids and optic vesicle-containing brain organoids (OVB-organoids), and performed multiscale analyses using immunofluorescence and transcriptomics to compare the two models. Key differences in cellular composition, structure, function and development were found; OVB-organoids better simulated early retinal development, visual-related structures/functions, with specific VSX2 expression and consistent transcriptomic profiles. OVB-organoids are an improved model for early neurodevelopment, providing a reliable basis for exploring eye-brain coordinated development mechanisms and having broad applications in developmental biology, disease research and personalized healthcare.