The brain is a well-organized organ consisting of telencephalon, diencephalon, mesencephalon, and metencephalon. Each brain region has specific functions and interacts with other regions by neuronal axons and synaptic connections. Thus, region-specific neuronal differentiation from human pluripotent stem cells would help for better understanding human brain development and the pathogenesis of various neurological diseases, and for use in drug development, disease modeling and regenerative therapies.
Recently, we analyzed gene expression profile of human developing ventral midbrain by single-cell RNA-sequencing and established new protocol for generation of midbrain dopaminergic (DA) neurons from human embryonic stem cells by modification of crucial morphogenic factors and transcription factors. In addition, we generated brain organoid that is co-cultured with human induced pluripotent stem cells (hiPSCs)-derived neurons and microglial progenitor cells. We also generated multiregional assembloid that mimics the neural network formation of nigrostriatal pathway and the pathogenesis of Parkinson‘s disease (PD). using region-specific differentiation technology. Furthermore, we will introduce new therapeutic advantage of medicine for promoting synaptic formation of grafted hiPSC-derived DA neurons towards more beneficial cell transplantation therapy for PD.