Finally, to provide orthogonal validation of our findings in postmortem brain samples, and escape the known limitations of postmortem brain molecular analysis that until development of reprogramming technology has been the mainstay of functional analyses of molecular and cellular phenotypes in BD, we assessed the expression of miR-34a upon differentiation of human induced pluripotent stem cell (iPSC)-derived NPCs (hNPCs) generated from one BD patient (Madison et al., manuscript under revision in Molecular Psychiatry) and their healthy parental (father) as a control31. The level of neuronal differentiation was evaluated by measuring multiple differentiation markers at different developmental stages (Figures 1C-D and S2A-F). Of note, both hNPC lines express the neural progenitor marker Nestin at similar level (Figure S2G). We found that miR-34a was expressed at low levels in hNPCs, and was modestly upregulated upon differentiation (Figure 1E). Unexpectedly, BD-derived hNPCs and 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
