In summary, with the generation of this set of 12 iPSCs along with a set of representative expandable NPC lines for the first time from a family with BD, our studies have established a new paradigm and resource for gaining insight into the etiology and pathogenesis of BD. Collectively, our phenotypic comparisons present numerous avenues for future investigation through the implication of abnormalities in early steps in NPC formation, WNT/GSK3 signaling, and ion channels expression in the BD patient-derived NPCs and neurons. Future expansion of these studies to include samples from additional families and well phenotyped patients along with appropriately selected controls holds tremendous promise for helping elucidate fundamental mechanisms of human disease biology and for presenting a new path for translating basic research into novel therapeutic discoveries for BD74.
