Here, we describe a 3-D culture system for generating human brain organoids resembling the MGE domain (human MGE organoids; hMGEOs) and cortical domain (human cortical organoids; hCOs). hMGEOs and hCOs displayed cellular organizations similar with developing MGE and cortex, respectively. Cells interior of hMGEOs and hCOs efficiently developed neuronal activity. We performed transcriptome profiling utilizing developing hMGEOs and hCOs in parallel to examine their dynamics. Furthermore, genome-wide chromatin accessibility landscapes were characterized for hMGEOs and hCOs to investigate transcriptional regulation mechanism. Moreover, we profiled single cell transcriptome of developing hMGEOs and hCOs. Finally, we describe a 3-D approach to assay human interneuron migration by fusing hMGEOs with hCOs to produce human fused MGE-cortical organoids (hfMCOs).
