Fig. 7: Comparative analysis of transcriptome and methylome of GIC/iNSC identifies NTRK2/CTX as patient-specific drug sensitivity.
a Drug treatment of GIC (black curves) and iNSC (grey curves) of patient 30 (top) and 18 (bottom) with doses ranging from 1 nM to 10 µM of CTXB (blue dots) or vehicle (black dots). Results are expressed in percentage of viability on the vehicle and were measured at end point, area under the curve (AUC) was calculated from percentages of viability (n = 6 experiment repetitions,two tailed t-test, p value (patient 30) = 0.0326, p value (patient 18) = 0.5394). b Proliferation assay of GIC30 (top) and 18 (bottom) treated with vehicle (black bars) or CTX-B (blue hatched bars) assessed by cell numbers after 4 days of culture. Results are expressed as fold change of cell number at day 4 on day 1 of treatment and standardized on the vehicle treatment conditions (n = 3 experiment repetitions, two-tailed t-test, p value (GIC 30) = 0,0080, p value (GIC 18) = 0.9363). Viability of total cells of SYNGLICO (cerebral organoids (CO) + GICGFP) after 4 days of treatment with vehicle or CTX-B (50 µM, 100 µM) (c) and GFP Mean Fluorescence Intensity (MFI) of GICGFP+ cells (d) (COGIC30 vehicle: n = 10, CTX-B 50 and 100 µM: n = 9; COGIC18: n = 7 SYNGLICOs per group, one way ANOVA, two-sided. c Patient 30: p value (Vehicle vs CTX-B 100 µM = 0.3759); d Patient 30: p value (Vehicle vs CTX-B 100 µM = 0.0230). e Survival curve of mice bearing GIC30-derived (left) and GIC18-derived (right) intracerebral xenograft treated with vehicle (n = 7) or tat-Cyclotraxin-B (n = 8), log-rank (Mantel−Cox), two-sided, p value (GIC 30) = 0.0290. All graphs report mean ± SEM. Statistical significance for all panels *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001. Source data are provided in the source data file.
