Previous reports of hiPSCs and differentiated neurons, which were derived from patients with schizophrenia, demonstrated several abnormal phenotypes in vitro.18, 20, 28, 29, 30, 31 We performed neurosphere formation assays using control- and patient-derived hiPSCs. The size and number of neurospheres were measured on the 14th day after passage (Figure 1a). The neurospheres expressed the neural stem cell marker SOX2 (Figure 1a). The mean size of neurospheres generated from patient-derived hiPSCs was reduced by 30% compared with that of control hiPSCs (P<0.0001; Figures 1a and b). We also found that the number of spheres with a diameter of less than 100 μm was significantly increased among patient-derived neurospheres (P=0.0046), whereas the number of neurospheres with a diameter of more than 200 μm was significantly decreased among patient-derived neurospheres (P=0.0265; Figure 1c). However, the total numbers of neurospheres generated from control hiPSCs and patient-derived hiPSCs did not differ significantly (Figure 1d). Importantly, the reduction in the size of neurospheres is also reported for neurospheres generated from the hippocampus of Dgcr8 heterozygous knockout (Dgcr8+/−) mice.10
