In vitroスクリーニング利用を目指したロバストな神経サブタイプ分化プラットフォームの構築

抄録

It has already become a powerful tool for generating neural cells from human induced-pluripotent stem cells (iPSCs) to mimic neurophysiological functions, for instance, by constructing brain organoids. In particular, recent studies using disease-specific iPSCs cells have also been required to utilize a large number of samples, including sporadic diseases. In addition, it becomes important to validate pathological conditions and drug screening in a rapid manner. However, required long period culture, highly cellular heterogeneity and highly clonal diversity make analysis of brain organoids difficult. Therefore, an application of alternative rapid and accurate method has been needed, so target-specific neuronal induction by transient expression of bHLH-type proneural factors and other transcription factors in iPSCs can be very useful.

We have improved this tool based on using TetO-Neurog2 or TetO-Ascl1 system and developed a platform for stable generation and functional analysis of target neuronal cells. In this symposium, we will introduce our new platform and report the results of the studies on Alzheimer's disease and various psychiatric and neurodevelopmental disorders. We believe that our platform will enable us to selectively generate numerous subtype-specific neuronal cells and provide a rapid pathophysiological or drug screening system.