neurons expressed significantly more miR-34a levels in comparison with the WT unaffected relative control samples. To complement these iPSC-based findings with a different, and a larger, set of control and patient-derived cellular models of BD, we turned to the use of newly developed, direct reprogramming methods to create induced neurons (iNs)33. As shown in Figure 1F, iNs were generated through the transdifferentiation of human fibroblasts derived from BD patients and psychiatrically-screened healthy controls. Similar to our findings comparing the healthy parental iPSC-derived neurons to those of the BD patient son, we found a significant increase in miR-34a expression in iNs derived from BD patients compared to healthy control cultures (Figure 1G). Taken together, these postmortem and cellular data, which have allowed the analysis of the molecular profiles of live human neurons generated using two different reprogramming approaches, suggest that miR-34a expression is dysregulated in the context of BD.
