Advances in the pathophysiological study of brain development: application of cerebral organoid combined with Spatial omics technology.

Understanding the complexities of the human brain development remains one of the most formidable challenges in neuroscience, constrained by the limitations of traditional models and the inaccessibility of brain tissue. The advent of cerebral organoids has provided a transformative in vitro model that closely mimics the early stages of brain development, including the spatiotemporal organization and cellular heterogeneity. Derived from pluripotent stem cells, these self-assembling three-dimensional structures address critical limitations of earlier systems, including species-specific differences in animal studies and the structural constraints of conventional cell models. Over the past decade, cerebral organoids have enabled significant advances in studying neural development, neurogenesis, modeling neuroconnectivity, and investigating neuroregeneration. Meanwhile, high-throughput spatial multi-omics technologies have emerged for decoding molecular and cellular dynamics with spatial precision. These techniques retain the architectural context of biological samples while integrating diverse layers of omic information, providing unprecedented insights into tissue organization and interactions. By addressing the complexity of brain organization and facilitating actionable insights into neurodevelopmental diseases, this integration facilitates high-throughput drug screening, identifies disease-specific targets, and offers a path to novel therapeutic strategies and regenerative solution for future stem cell therapies for pediatric neurodevelopmental diseases.