Fig. 2: Developing tumours induce axonal injury in the WM.

a, Identification of myelinated regions. Top, H&E images of normal mouse brain (control) and the PDX model GCGR-L5 at the early (GCGR L5 early) and terminal (GCGR L5 terminal) stages. Bottom, as described for the top but overlayed with labels for high (green) and low (white) myelin marker genes expressing spots derived from ST data (Methods). Scale bars, 1 mm. b, Heat map of five k-mean clusters of log₂-transformed fold changes (log₂[FC]) from mouse genes significantly regulated between WM and GM in control, early and terminal PDX tumour ST spots (Methods). Selected terms enriched in cluster five are shown on the right. c, Gene set enrichment analysis in WM ST spots from control brain, or early and terminal PDX tumours. Normalized enrichment scores (NESs) of significantly enriched GO terms are shown (adjusted P < 0.1). d, Gene set enrichment analysis as in c, for cell type markers from ref. ⁵¹. The median of enrichment values across PDX models is shown. Astro, astrocytes; DC, dendritic cells; EC, endothelial cells; oligo, oligodendrocytes. e, The proportion of myelin high/low spots in bins of increasing tumour density (top). Middle, the proportion of spots assigned to anatomic brain regions in bins of increasing tumour density. Bottom, the average gene expression of functional categories in spots in bins of increasing density. f, The proportion of different cell types in bins of increasing tumour density derived by deconvolution using published scRNA-seq datasets (Methods). g, Reanalysis of ST data from ref. ²⁶. Top, the proportion of spots assigned to histological regions in bins of increasing tumour density. Bottom, the averaged gene expression of different functional categories in bins of increasing tumour density.