Figure 7.

SOX6-mediated induction of metabolic pathways provides protection of neurons to mitochondrial toxicity

(A) Proteins differentially expressed between L-SOX6 (red bars) and L-OTX2 (blue bars) transduced hESC-derived cultures (day 35). Expression levels are presented as log₂ transformed fold change (FC) values.

(B) Graph indicates pathways significantly enriched in L-SOX6 and L-OTX2 transduced cultures.

(C) IHC analysis of L-SOX6 transduced hESC-derived cultures treated as indicated for 24 h at day 35. Arrows indicate cCASP3-labeled SOX6- and TH-expressing neurons.

(D) Relative ATP levels in rotenone- and 6PG-treated cultures (24 h, day 35) as a percentage of the untreated cultures. Mean ± SD; one-way ANOVA with Bonferroni correction; n = 4 independent experiments.

(E) Percentage of cCASP3-, SOX6-, and TH-expressing cells in hESC-derived L-SOX6 transduced cultures treated with rotenone and meclizine (24 h, day 35). Mean ± SD; one-way ANOVA with Bonferroni correction; n = 4 independent experiments.

(F) mESC differentiation scheme. IHC analysis of Nes-Lmx1a mESC-derived cultures. Arrows indicate overlap between cCASP3 and TH.

(G) Percentage of TH⁺ neurons present in mESC medial FP-derived cultures. Control value normalized to 100. Mean ± SD; one-way ANOVA with Bonferroni correction; n = 4 independent experiments.

(H) Model illustrating DA sublineage selection process during mouse and human PSC differentiation and its consequences on vulnerability.

^∗p < 0.05, ^∗∗p < 0.01, ^∗∗∗p < 0.001. Scale bars, 50 μm.