Fig. 7: Netrin-1 is a survival factor in proliferative cells upon anti-SMO treatment.

a t-SNE projection of tumor cells from the spontaneous Math1-Cre/SmoM2 SHH MB mouse model (M-Smo mice) treated with vehicle (n = 5) or Vismodegib (n = 5), based on PCA and color-coded for the expression of indicated markers. Metaclusters are defined by hierarchical clustering of single-cell RNA clusters. The percentage of cells expressing the genes of interest are quantified in the proliferative (green), intermediate (blue) and differentiating (purple) subsets. Analyses were performed using previously published single-cell RNA sequencing (scRNA-seq) data⁴⁰. b Representation of calculated synergy maps (3D above and 2D below) based on dose response matrix. Primary murine SHH MB cells, from the hGFAP-Cre/SmoM2 (G-Smo) model, were treated with a range of NP137, GDC-0449, or a combination of both drugs in an 5 × 5 matrix as indicated, for 72h, followed by a luminescence-based assay for cell viability. Synergy score was calculated using the HSA reference model. Negative scores indicate antagonism (green) and positive scores indicate synergy (red). Results are representative of three independent experiments.