One gene identified as down regulated in the BD patient CXCR4+ NPCs in the RNA-seq profiles that was found to be significantly highly connected (p<0.005; 5,000 permutations) within the DAPPLE network was that of Wingless-Type MMTV integration site family, member 7B (WNT7B), which had direct interactions with four other seed nodes consisting of two members of the frizzled family of seven transmembrane receptors (FZD5, FZD7) and two soluble frizzled-related proteins (SFRP1, SFRP2) (Fig. 5E). Collectively, the proteins within this module are known to play key roles in the regulation of WNT signaling, which is known as critical mediator of neurogenesis, neurodevelopment, and synaptic plasticity. Motivated by these observations, the previously observed differential expression of multiple WNT pathway components in both the PsychGene NanoString profiles (Fig. 5A, B), along with previous implication of WNT/GSK3 signaling in BD in part through the ability of lithium to activate WNT signaling12–14, we hypothesized that activation of WNT signaling through GSK3 inhibition would be sufficient to rescue the NPC proliferation deficits observed in the FACS-purified, BD patient-derived CXCR4+. In agreement with this notion, as shown
