we used this differentiation paradigm on SCZD patient hiPSCs and control hiPSCs as a proof-of-principle application. We found deficits in the generation of hippocampal granule neurons from SCZD hiPSC-derived hippocampal NPCs with reduced levels of PROX1 and TBR1. Furthermore, SCZD granule neurons showed deficits in neuronal activity, as evidenced by the reduced frequency of spontaneous neurotransmitter release. Our strategy to generate a specific, disease-relevant subtype of neurons reduces the variability within the cellular population being examined and allows for the detection of early alterations in the developing SCZD hippocampal granule neurons. This approach may offer important insights into the neurodevelopmental aspects of SCZD and presents a promising tool for drug screening, diagnosis, and personalized medicine.
