From gene expression in comparisons with the Allen BrainSpan Atlas, we demonstrate that hiPSC forebrain NPCs and 6-week-old neurons more closely resemble fetal brain tissue. Although our extensive characterization of spatial and temporal identity revealed that hiPSC NPCs show inter-cell and inter-line heterogeneity, variation between hiPSC NPCs lines does not explain the consistent SZ-associated hiPSC NPC phenotypes observed. Using two unbiased discovery-based approaches, microarray gene expression and SILAC quantitative proteomic mass spectrometry, we predicted, and observed, aberrant migration and increased oxidative stress in a pilot cohort of SZ hiPSC NPCs, although effect sizes were insufficient to predict diagnosis. We are the first to report aberrant migration in SZ hiPSC neural cells, and we have doubled the number of SZ patients from which hiPSC neural cells show increased oxidative stress.17,21 We conclude that gene expression and proteomic data sets can be used to identify novel cellular phenotypes of SZ, but we caution that, because of our small sample size, these phenotypes may not generalize across all SZ patients.
