Chunk #28 — Results — Organoids derived from schizophrenia iPSCs—dispersion of proliferating cells in the cortex and blockade of cortical neuronal development
After establishing the protocol for the generation of hESC cerebral organoids, we applied this procedure to human iPSCs. To analyze whether early brain development may be altered in schizophrenia, we used iPSC lines reprogrammed from three schizophrenia and four control individuals, in which common dysregulated transcriptomes have been recently identified29. Our qualitative observations were verified by computational and statistical analyses of three schizophrenia and four control patients and are described below. In general, the iPSC cerebral organoids followed the developmental pattern and displayed cortical rosettes that were similar to the hESC organoids. At 5 weeks, the rosettes of both control and schizophrenia iPSC organoids had only narrow residual lumens (Supplementary Fig. 2). No gross size differences were observed between control and schizophrenia iPSC organoids. However, a detailed cellular analysis revealed marked differences between control and schizophrenia organoids (Fig. 2). The control iPSC organoids, similar to hESC organoids, contained 2–3 layers of proliferating Ki67+ NPCs in the VZ, few Ki67+ cells in the IZ, and none or only single proliferating cells in the CZ. These layers were already observed at week
