Extended Data Fig. 9: Neuronal localization and distribution across transcriptomic niches.

a. Spatial metabolomics examining adenosine (m/z: 268.09 adducts: M + H) in participant A-05 tumor. Detected intensity score, above, 3D density map extrapolated from intensity, below. Scale, 1 mm. b. Enrichment heat map of each cell type identified co-localized within the transcriptional niches. c. Overlayed immunofluorescence, cell types and transcript niches in participant O-01 pre- and post-safusidenib (n = 3 per condition). Scales depicted in relevant immunofluorescence inset (left), 1000 µm, 100 µm and 10 µm. Immunofluorescence: DAPI, blue; GFAP, green; Phalloidin, magenta. Cell type annotations with immunofluorescence overlay (bottom right panel) and Niche subsets with immunofluorescence overlay (bottom right panel). d. Spatial maps of participant A-05 post-safusidenib sample indicating presence of neurons (red) with associated density contour plot (left) and showing cells expressing key neuronal layer markers (right) profiled with Xenium. Scale 1 mm. e. UMAP of neurons colored by neuron cell annotation (left). Box plot of synaptic signaling average log expression for each participant in different neuron populations pre- and post-safusidenib. Box indicates IQR, centre line is median; whiskers extend to the furthest points within 1.5 × IQR.