Importantly, we found oligodendrocyte progenitors (OPC1-2, marked by S100A10 and CD44) arose mostly from hMGEOs, and until late stage, only a limited number of OPCs were produced from hCOs (Fig. 5H). Meanwhile, mature oligodendrocytes (OL) were exclusively produced from hMGEOs. To confirm this differential pattern of oligodendrocyte formation in hMGEOs and hCOs, we mapped single cell transcriptome of primary AS, OPC and OL from published human brain tissues (Darmanis et al., 2015), and found AS, OPC and OL produced from hMGEOs displayed significant correlation with their in vivo counterparts (Figure S4E). Furthermore, immunostaining for OLIG1 in late stage (day 81) organoids confirmed that OLIG1+ cells were uniquely produced in hMGEOs (Figure 5I). Similarly, previous neurodevelopmental studies in mouse identified the first OPC wave in MGE and entopeduncular area of ventral forebrain (Kessaris et al., 2006). Thus, our results suggest that during human brain development MGE and cortex also display distinct timelines for oligodendrocyte genesis, with oligodendrocyte genesis from MGE preceding the cortex.
