0.05, Benjamini-Hochberg corrected) (Fig. 4C; Fig. 5B). Given the desire to gain insight into specific neuronal subtypes that may underlie alterations in the neurocircuitry affected in BD, analysis of the expression of markers of specific neuron subtypes revealed differential expression of only the cortical layer maker CTIP2 (BCL11B) and RELN, which were both significantly downregulated in the BD-patient neurons compared to neurons from the unaffected parents (Fig. 4C; 5B), while numerous other markers of defined neuronal subtypes showed no difference (Sup. Fig. 11). In this context, CTIP2 is notable as it is a component of the nucleosome remodeling and deacetylation (NuRD) complex48, which plays a key role in the epigenetic regulation of neurogenesis49 and the differentiation of cortical layer V/VI subcerebral projection neurons50. RELN, an extracellular matrix glycoprotein, in contrast, is involved in cortical neuron migration51. Taken together, these results provide further support for our hypothesis that differentiation into specific neural lineages is disrupted in the BD-patient iPSCs when comparing FACS-purified CXCR4+ NPCs.
