Designing reverse genetic experiments to ascertain the function of SZ-associated genes is hampered by the paucity of (and inability to manipulate) postmortem tissue from SZ patients. Human-induced pluripotent stem cell (hiPSC)-derived neural cells represent a novel strategy by which to model the genes underlying SZ predisposition. Using hiPSC-derived neural cells, we have previously demonstrated aberrant gene expression, protein levels and migration in SZ hiPSC-derived neural progenitor cells (NPCs) (Brennand et al., 2015, Topol et al., 2015, Topol et al., 2016), and diminished neuronal connectivity and synaptic activity in SZ hiPSC-derived neurons (Brennand et al., 2011, Yu et al., 2014). Although these hiPSC-based studies partially reflect postmortem pathological (Wong and Van Tol, 2003) and SZ-rodent model (well-reviewed by Jaaro-Peled et al., 2010) findings, the precise functional dissection of SZ “risk genes” in hiPSC neuronal models has been challenging, except for small studies of rare families with SZ-associated inherited mutations (Lin et al., 2016, Srikanth et al., 2015, Wen et al., 2014, Yoon et al., 2014, Zhao et al., 2015). The ability to precisely modulate SZ disease-relevant gene expression in hiPSC-derived neural
