To begin to explore the potential utility of such a family-based paradigm for iPSC-based modeling of BD, which to date has not been applied to any human genetic disorder, here we generated and characterized 12 iPSC lines from a family with two unaffected parents and two BD male offspring. Overall, while no significant differences were observed between the 12 iPSCs, upon directed differentiation to the neural lineage our studies revealed several neurodevelopmental phenotypes in both BD-patient cells compared to the phenotypes of their unaffected parents. Additionally, specific defects in the expression of genes important for neurogenesis and neuroplasticity were observed, thereby pointing to new pathways to explore in order to understand the neural substrates of BD pathophysiology and providing new cellular tools for novel therapeutic discovery.
