Fig. 6: Modulation of KAT5 activity in GSC-derived tumors and during GSC invasion assays.

a Scheme for using C13 GSC-0827 cells for creating PDX tumors in NSG mice. Created in BioRender. Paddison, P. (2025) https://BioRender.com/tehoi00. b Representative MRI image of mouse head with Dox-KAT5 tumor in cortex at 36 days post-injection. c Analysis of p27 levels after Dox withdrawal in C13 tumor containing mouse. KS test was used to test significance (p < 0.0001). d Analysis of EdU incorporation (6 h) after 7 days of Dox withdrawal in C13 tumor containing mouse. KS test was used to test significance (p < 0.0001). e Tumor growth as assessed by volume using MRI in C13-induced PDX tumors after switching drinking water to concentration of Dox indicated (µg/mL). Linear regression analysis was used to assess significance (p val overall = 0.001; p val2000 vs. 200 < 0.0001; p val2000 vs. 20 = 0.0049; p val2000 vs. 0 = 0.0183). f EdU incorporation for 20 h at 14 days after Dox concentration from (e). KS test was used to test significance (p < 0.0001). g C13 xenografts were treated with standard of care (SOC) in the presence (Dox + ) and/or absence (Dox–) of KAT5. Tumor growth was assessed by volume using MRI. The plot represents a linear regression analysis with the first MRI time point at enrollment of mice in experimental cohorts. The asterisk denote statistically significant differences between pairs of slopes for the indicated experimental conditions by color (nDox + = 8, nDox- = 8, nDox + /SOC = 9, nDox-/SOC = 5). Plots show mean ± SEMs. with simple linear regression curve comparisons for significance. h Kaplan-Meier survival probability plot for tumor bearing mice from (g). Survival probability differences between paired comparisons was assessed by log rank (Mantel-Cox) test. The asterisk denote statistically significant differences between pairs of comparisons for the indicated experimental conditions by color. Average survival days gained: Dox- = 17.75; SOC/Dox + = 17.97; and SOC/Dox- = 39.55. i, j KAT5^on vs. KAT5^off C13 invasion assays. C13 cells were grown as spheres for 3 days in either 1μg/ml Doxycycline for KAT5^on or no Doxycycline for KAT5^off conditions and transferred to Matrigel covered wells for the specified number of days (3 d, 7 d, or 9 d). Phase-contrast images were captured every 24 h for 72 h. The area covered by invading cells was measured using FIJI. i Representative phase contrast microscopy images of invasion assay. Spheroids were embedded into Matrigel. Scale bar is 200 μm. j Quantification of (e). n_KAT5on = 3, n_{KAT5off 3d} = 3, n_{KAT5off 7d} = 4, n_{KAT5off 9d} = 5. Mean ± SEM shown (significance was tested using repeated measurements 2-way ANOVA with Giesser-Greenhouse correction and Sidak multiple corrections test; p ≤ 0.01). Additional isolates are assayed in Supplementary Fig. 13. Source data with exact p values are provided with this paper as a Source Data file.