We found hMGEOs and hCOs recapitulated transcriptome features of developing human MGE and cortex domains. ATAC-seq confirmed the chromatin re-organization during organoid development in line with the global transcriptional changes. hMGEOs and hCOs generate multiple cells types whose identities were delineated by scRNA-seq (Figure 5). Similarly, recent study by Quadrato et al demonstrated a production of diverse cell types within organoids related with endogenous classes for cerebral cortex or retina using scRNA-seq (Quadrato et al., 2017). In addition to the well-defined neuronal and neuroprogenitor cell types, we identified the metabolically unique intermediate clusters that may represent the neural progenitors in a transition of glycolytic to neural oxidative phosphorylation (Figure 5H). scRNA-seq also distinguished the features of interneurons generated from hMGEO and hCOs. Interneurons from hMGEOs maintained the expression of NKX2-1 even after further development, while those from hCOs showed no expression of NKX2-1. Difference in developmental timing of oligodentrocyte progenitors and oligodendrocytes was remarkable in late hMGEO and hCO (Figure 5H), validating the concept of oligodendrocyte waves (Kessaris et al., 2006) in a human model.
