Fig. 5: Sarm1 deletion inhibits GBM progression and ameliorates neurological function.
From: Axonal injury is a targetable driver of glioblastoma progression
a–c, Representative images of tdTomato+ terminal WT and Sarm1−/− npp tumours (a), quantification of the proportions of tumours with defined bulk (localized) or diffuse phenotype (diffuse) (b) and the tumour cell density in each genotype (c). For a, scale bars, 1 mm. Data are mean ± s.d. Statistical analysis was performed using two-sided unpaired t-tests. n = 10 (WT) and n = 9 (Sarm1−/−) mice. d, Quantification of the tdTomato+ area in WT and Sarm1−/− terminal tumours. Data are mean ± s.d. Statistical analysis was performed using two-sided unpaired t-tests. n = 10 (WT) and n = 6 (Sarm1−/−) mice. e, Uniform manifold approximation and projection (UMAP) of scRNA-seq data from terminal WT and Sarm1−/− npp tumours: neural progenitor-like (NPC-like), OPC-like, astrocyte-like (AC-like), MES-like and aNSC-like. f, As in e, but for microenvironmental cells: choroid plexus cells (CP), astrocytes, inflamed glia (infl. glia), OPCs, transient amplifying progenitors/neuroblasts (TAP/NB), aNSCs, ependymal cells (EpC), endothelial cells, pericytes, TAMs, monocytes (Mn) and T cells. g,h, The proportion of subpopulations between genotypes in tumour (g) and non-tumour (h) cell populations. The dashed line denotes equal proportions. Pearson’s χ2 test < 0.05 and relative difference > 10% were considered to be significant (indicated by the hash symbol (#)). i–m, Flow cytometry analysis of immune populations (CD45 (i), TAMs (j), microglia (k), macrophages (l) and lymphocytes (m)) in terminal WT and Sarm1−/− npp tumours. Data are mean ± s.d. Statistical analysis was performed using two-sided unpaired t-tests. n = 5 (WT) and n = 4 (Sarm1−/−) mice. n, Kaplan–Meier analysis of npp tumour-bearing WT (grey) and Sarm1−/− (turquoise) mice. Median survival: 125 (WT) and 148 (Sarm1−/−) days. Statistical analysis was performed using log-rank tests. n = 22 (WT) and n = 18 (Sarm1−/−) mice. o, Neuroscores of npp tumour-bearing WT (grey) and Sarm1−/− (turquoise) mice at the indicated timepoints. Statistical analysis was performed using two-way ANOVA with Tukey’s multiple-comparison correction. Data are mean ± s.d. n = 5 (WT) and n = 5 (Sarm1−/−) mice. p, As for n, but for Sarm1-WT (WT, grey) and Sarm1em1.1Tftc (turquoise) mice. Median survival: 120 (WT) and 152.5 (Sarm1em1.1Tftc) days. Black lines denote censored animals. Statistical analysis was performed using log-rank tests. n = 10 (WT) and n = 12 (Sarm1em1.1Tftc) mice. q, As described for o, but for Sarm1-WT (grey) and Sarm1em1.1Tftc (turquoise) mice. Statistical analysis was performed using two-way ANOVA with Tukey’s multiple-comparison correction. Data are mean ± s.d. Early: n = 8 (WT), n = 13 (Sarm1em1.1Tftc); advanced: n = 6 (WT) and n = 11 (Sarm1em1.1Tftc) mice.
