Having demonstrated that manipulation of miR-34a expression in human iPSC-derived NPCs causes aberrant expression of synaptic proteins and the establishment of morphologically complex neurons, we sought next to determine the effects of miR-34a expression on a broader set of 18 genes implicated in neuropsychiatric disorders and neurodevelopment by recent GWAS of BD, as well as SYP and SYN1 as controls based upon our Western blot data showing synaptic dysregulation (Figure 4, Figures S4–S6, Tables S8–S10 and Supplementary text). Using a multiplexed, digital, mRNA profiling assay based upon NanoString single molecule, direct mRNA counting technology, among the genes we tested, miR-34a overexpression significantly affected the expression of 9 genes (SYNE1, CACNA1C, CACNB3, SYN1, TNR, SYT12, SYP, ANK3, TMEM110), with ODZ4 and ITIH4 close to having a significant difference (Figures 4A and S4).
