Fig. 6: Progenitor cancer cells are drivers of chemoresistance and tumor growth.

a Box–whisker plots showing the proportion of viable glioma stem cells (GSCs, n = 1 patient: BT390-GSC) sorted by type and followed by 5 days of temozolomide (TMZ) treatment, normalized to corresponding vehicle control. See Supplementary Fig. 5e for additional patients. Three technical replicates and three biological replicates were performed per condition. Box plot represents the first quartile, median, and third quartile with whiskers corresponding to 1.5 times the interquartile range. The overlaid dot-plots represent the mean value per biological replicate per group. A one-tailed, two-sample equal variance t test was used. b Select bioluminescence images from mice implanted with GSCs sorted by type. Mice implanted with progenitor GSCs exhibit a more rapid tumor growth compared with those implanted with neuronal or astrocytic GSCs. c Average bioluminescence intensity over time for mice xenografts injected with different GSC types sorted from BT333-GSC (n = 24). Data are represented as mean ± SE. p values obtained with two-tailed, two-sample t tests. d Mice from each GSC group was killed at 12 weeks and the corresponding H&E and immunofluorescence images for cell type markers are shown. Expression of cell type-specific markers was quantified from ~1000 to ~3000 human nucleoli (hNu)-positive cells per mouse model group. Each graph represents n = 2 biologically independent mouse brain sections. Scale bars: whole mount images: 1 mm; immunofluorescence images: 50 μm. e Kaplan–Meier survival curves for mice implanted with different GSC types (n = 47). Univariate Cox proportional Hazard Model (two-sided) shows a significant difference in survival between progenitor GSC and neuronal (p value = 0.0025) or astrocytic GSC (p value = 5.7e-6) xenografts, and also between neuronal and astrocytic GSC xenografts (p value = 0.0059). For all plots, ***p < 0.001, **p < 0.01, *p < 0.05.