Skip to main content
. Author manuscript; available in PMC: 2021 May 19.
Published in final edited form as: Cell Rep. 2021 Apr 13;35(2):108991. doi: 10.1016/j.celrep.2021.108991

Figure 4. Overactive PI3K signaling links translational dysregulation and aberrant proliferation in FXS-patient-derived cells.

Figure 4.

(A) Representative overlaid dot plots of one control (gray) and one FXS NPC line (red) showing puromycin and Ki67 signals. FXS NPCs have more Ki67+ cells and increased protein synthesis (Mann-Whitney test, *p < 0.05, n = 3 CTR, 3 FXS lines; each data point represents an average of two experimental replicates).

(B) Representative images of NPCs stained for Ki67, pHH3 and DAPI after treatment with p110β inhibitor (TGX) and S6K1 inhibitors (PF). Scale bar, 50 μm.

(C and D) Treatment with either inhibitor normalizes aberrant proliferation in FXS NPCs (n = 4 CTR, 4 FXS NPCs; two-way ANOVA, Tukey’s test, *adjusted p < 0.05, **adjusted p < 0.01, ***adjusted p < 0.001, ****adjusted p < 0.0001).

(E) Chronic (12-day) treatment using TGX normalizes increased abundance and corrects elevated protein synthesis in proliferating cell populations in FXS cultures. TGX does not significantly alter abundance of non-proliferating cell populations, although they trended toward increased abundance. (n = 4 CTR, 4 FXS NPCs; two-way ANOVA, Tukey’s test, *adjusted p < 0.05, **adjusted p < 0.01, ***adjusted p < 0.001). All data are shown as means ± SEM.