Fig. 5: In vivo models of radiation resistance.

A Schematic of the radiation resistance model development. Created in BioRender. Vibhakar, R. (2025) https://BioRender.com/miahqmf. B UMAP visualization of control tumors(n = 2) and radiation-resistant tumors (n = 4). Total cells (n = 15982). C Cell grouping of clusters is based on ORA GSEA. Color designation is based on clustering. Control tumors(n = 2) and radiation-resistant tumors (n = 4). Total cells (n = 15982). D Heatmap of top 10 DEGs by cluster. Control tumors(n = 2) and radiation-resistant tumors (n = 4). E Over-representation analysis (ORA) heatmap based on individual clusters. Control tumors (n = 2) and radiation-resistant tumors (n = 4). F GSEA comparing radiation-resistant tumors (n = 4) to control (n = 2). The top 10 gene sets with >1 Normalized Enrichment Scores and <−1 are shown. p < 0.001. P-value is calculated by a permutation test. G UMAP visualization of PDX411 radiation-resistant tumors (914, 915, 916); (n = 3) and 411FH control (Hovestadt) and 918 (n = 2). Total nuclei =12614. H Progenitor-photoreceptor gene signature expression on UMAP of PDX411 radiation resistant (n = 3) and 411FH control (n = 2). Color scale indicates Log2 gene expression. Total nuclei n = 12614. I Violin plot of Progenitor-photoreceptor gene signature expression in radiation-resistant tumors (n = 3) compared to control (n = 2). The widest part of the violin plot corresponds with the average single-cell expression levels. J Heatmap of top three DEGs by cluster in PDX411 tumors (n = 5). Gene expression color indicates Log2 scale. K Gene ontology analysis of the top 100 genes in cluster 6. Significant GO enrichment terms are determined by the hypergeometric distribution and reported as -Log₁₀(Pval). L Functional enrichment on genomic regions associated with gained peaks (n = 195098 genomic regions). Metabolic and epigenetic associations are highlighted in color. Significance of enrichment is determined by a binomial test after multiple testing correction (false discovery rate) applied, shown as -Log₁₀(Binomial FDR Q). M UMAP visualization of ATAC-seq clusters from radiation-resistant tumors (n = 3) and control (n = 1). Total nuclei = 12528. The progenitor-photoreceptor and cycling neural progenitor gene expression signatures are mapped onto clusters. Color scale indicates Log2 gene expression. (Left) Representative ATAC peak profile for NFE2L2 accessibility in radiation-resistant (n = 3) and control (n = 1) tumors by cluster. Link arc plot is shown between peaks, Significance reported as -Log₁₀(Pval)=9.43, correlation = 0.28. Linkage correlation, ranging from −1 to 1. Linkage significance: -log10 p-value after multiple testing correction (false discovery rate). Peaks are highlighted in black boxes. See also Supplementary Fig. 5.