Diverse approaches to neuronal cell culture from iPS cells: toward a model for neurodevelopmental disorders

The use of patient-derived iPS (induced-pluripotent stem) cells has become very meaningful for the development of pathological models and therapies for neuronal diseases. However, when modeling pathological conditions in vitro, it is very important to know which cell culture method to use. There are strong and weak points to each type of stem cell-based culture. We have been developing neuronal induction methods for pathological modeling of psychiatric and developmental disorders. In this study, we used both 2-D and 3-D cultures effectively. Directed neural differentiation by Dual SMAD inhibition and addition a morphogen allows us to observe neurogenesis-based tissue formation, which may reveal cellular phenotypes during development: this is achieved by 3D culture system. However, it is not always possible to obtain disease-causing cells under these conditions. In this case, it would be useful to use transient expression of transcription factors in iPS cells to directly differentiate into subtype-specific cells: this is achieved by 2D culture system. Each differentiation and culture technique is constantly evolving. It will be necessary to consider how to generate phenotypes more robustly. In this symposium, we introduce our research on modeling of psychiatric and developmental disorders based on customized neural differentiation system.