Long-term combination of ribociclib and gemcitabine increases the activity of genes involved in neuronal identity in G3MB. NetBID analysis and differentiation score of tumors from mice bearing PDOX MB002 (A–D) or mouse tumor #2416 (E–H) treated with vehicle (black bar), gemcitabine (blue bar), ribociclib (red bar), and gemcitabine and ribociclib (combination) (purple line). A and E, Activity heatmaps of a selection of genes from tumors for each treatment group. B and F, Volcano plots showing genes with differential activity in tumors treated with gemcitabine and ribociclib combination versus vehicle (network size > 25; P < 0.01 and logFC < -0.05 or logFC > 0.05). C and G, Clustering of genes in upregulated pathways. D and H, Differentiation scores for tumors for each treatment group computed from a single-cell RNA-seq dataset from the developing mouse cerebellum (Mann–Whitney test, gemcitabine + ribociclib versus vehicle).