Figure 1

(A) Schematic overview of key steps of the protocol used to derive cerebral organoids from hiPSC. The culture protocol promotes generation of organoids recapitulating dorsal pallial tissue differentiation. (B) Brightfield microscopic images of organoids at three stages of differentiation including EB stage on day 3 (scale bar: 200 µm), neuroepithelial stage on day 12 (scale bar: 500 µm) and neurogenesis stage on day 46 of culture (scale bar: 1 mm). (C) Scheme summarizing the laminar organization of cell types in 9-week old organoids. The ventricular zone (VZ) hosts radial glia cells (RGC), the main neural stem cell pool in cerebral organoids. Asymmetric divisions of RGC at the apical pole of the VZ yield intermediate progenitor cells (IPC) and outer RGC (oRGC) which migrate out of the VZ and populate apical (IPC) or more basal regions (oRGC) of the subventricular zone (SVZ). Newborn neurons generated by IPC and oRGC in the SVZ migrate to the cortical plate (CP) where early-born, deep layer (DL) neurons populate inner CP regions and later-born, upper layer (UL) neurons are enriched in the most peripheral CP regions. (D) Growth trajectory of organoids derived from BIHi001-B line during a 10-week culture experiment. Measurements of the diameter (in µm) of the cross-sectional area of phase contrast images are shown. Data presented are means ± standard deviations (N = 10–15 organoids per time point). (A) and (C) were created with BioRender.com.