Oligodendrocyte dysfunction and myelin deficits have also been heavily implicated in SZ by genome association and post-mortem studies (Burns et al., 2003; Davis et al., 2003; Tkachev et al., 2003; Takahashi et al., 2011; Goudriaan et al., 2014; Schizophrenia Working Group of the Psychiatric Genomics Consortium, 2014). Specifically, volume reduction in myelin observed in SZ patients is consistent with deficits in neuronal communication and synaptic plasticity thought to underlie SZ pathology (reviewed by Takahashi et al., 2011). A hiPSC model of patient oligodendrocytes and healthy neurons would allow to investigate the precise consequences of patient-specific variation in oligodendrocyte genes on myelin formation, interactions with neurons, and synaptic plasticity. Additionally, given the well-established role of myelin in neuronal maturation (Hasegawa et al., 1992), co-culture with oligodendrocytes will likely improve the immature state of current neural hiPSC cultures. Although to date no co-culture system of hiPSC-derived oligodendrocytes and neurons has been reported, oligodendrocytes have been successfully generated from hiPSCs (Livesey et al., 2016; Ehrlich et al., 2017). Most excitingly, Ehrlich et al. (2017) demonstrated successful integration of hiPSC-derived oligodendrocytes into mouse brains, giving hope that this myelination can be reiterated in vitro with human cells.
