Besides the cellular-level phenotypic differences in NPC formation and neurogenesis, at the molecular level several groups of differentially expressed genes were observed further supporting the notion of neurodevelopmental abnormalities in the BD-patient NPCs and neurons. Of note, CNTN6 (Contactin-6; NB-3), a cell adhesion molecule also implicated in autism71, which has shown modest association (rs3772277; p = 0.000126) with BD in the Psychiatric GWAS Consortium study70, and was significantly associated with a BD subgroup with co-morbidities in the GAIN cohort72 (rs2727943; p = 3.3×10−8) was among the most differentially expressed genes in both the NanoString and RNA-seq profiling (Fig. 4C; 5A, B). Previous work suggests that Contactin-6 plays a role in maturation of oligodendrocyte progenitors through its interaction with Notch1, a key regulator of neurogenesis73, potentially pointing to perturbation of oligodendrocyte development in the BD-patient iPSCs. Future studies aimed in investigating whether there are oligodendrocyte abnormalities in these and other BD iPSC models is warranted. Finally, several results from our studies suggest WNT signaling is perturbed in the neural cells from the two BD affected sons. First, in both our NPCs
