Figure 3.

PTM expression in HD180 iPSC-derived neural cultures reverses established mtHTT phenotypes. (A) ATP levels in HD and control NPCs. Cells were dissociated and ATP levels were assayed in equal numbers of cells. Control NPCs had significantly more ATP than HD NPCs. However, expression of PTMs significantly increased ATP levels in the HD, but not control, NPCs. Expression of GFP did not significantly affect ATP levels. ^***p < 0.001, ^****p < 0.0001, one-way ANOVA. Data are plotted as means and SEM. At least three separate passages of NPCs were examined. (B) HD and control iPSCs, with or without PTMs, were differentiated toward a striatal fate for 42 days before BDNF was withdrawn for 24 h. Cells were fixed, assayed for TUNEL, and counter stained with Hoechst. The percentage of TUNEL-positive nuclei was calculated as a measure of toxicity. The HD180 iPSC-derived striatal cells showed more cell death after BDNF withdrawal than did control iPSC-derived striatal cells. However, BDNF withdrawal in the presence of PTMs, but not GFP, reversed this toxicity. ^**p < 0.01, ^***p < 0.001, one-way ANOVA. Data are plotted as means and SEM. At least three fields per coverslip (three coverslips per experiment) were counted at random during at least three separate differentiation experiments.