To assess both the region specificity and maturity of our organoid preparation in a comprehensive fashion, we analyzed the global transcriptome of organoids by RNA-seq at each of three time points (rosette stage, TD11, and TD31, two to three iPSC lines per individual, total 45 samples). The organoid’s transcriptomes were compared with BrainSpan, the largest dataset of postmortem human brain transcriptomes from embryonic age to adulthood (Kang et al., 2011). This comparison indicated that our preparation best reflected the transcriptome of the human brain during early fetal human development (9 weeks post conception), with TD31 cells displaying significant correlations also with second trimester human brain samples, up to 13–16 weeks post-conception (Figure 1G). With regards to regional specification, the transcriptome of iPSC-derived organoids was most similar to the human dorsal telencephalon (cerebral cortex and hippocampus), particularly to dorsolateral, medial, and orbitofrontal cortical areas, with smaller but significant homology to the cerebellar anlage and the amygdala (Figure 1H, I).
