Although the generalizability of these observations will require the creation of iPSCs from additional BD patients, which is ongoing, two other studies in the context of psychiatric disorders that described the isolation of similar NPCs did not describe phenotypic defects in these types of cells25,61. While this manuscript was under revision, a study by Chen et al.62 described a set of BD patient-derived iPSCs. While Chen et al. did not characterize phenotypes of BD NPCs, when differentiated neuronal cells derived from neuronal rosettes were examined, encouragingly several gene expression changes that overlap with those identified in our iPSC-derived cells from Family-811 were observed. First, PAX6 gene expression was altered in both studies: Chen et al. showed PAX6 expression was decreased in BD patient neurons; our data suggest PAX6 expression is decreased in BD patient NPCs, but in our studies PAX6 expression in the culture was increased upon further differentiation into neurons (Fig. 5A, B). While the direction of the PAX6 effect in neurons is different, both of these BD iPSC studies are consistent with there being an alteration in the
