Fig. 3

a–c Representative low magnification images of 3 PN showing classic PN histology by H&E staining (left), including nerve fascicles with surrounding collagen tissue. In left panels (a, b), the fascicles are surrounded by perineurial fibrous capsule. Between the nerve fascicles is a more prototypical neurofibromatous proliferation. c (Panel left) depicts an example of PN architecture that is highly disorganized, with no discernable fascicle features, and highly intermixed cell types. On the right panel, corresponding H&E images with overlayed ST spot clusters revealing extensive heterogeneity of transcriptomic signatures across the TME, with endoneurial regions containing Schwann cells ad nerve cells, flanked by perineurial and epineurial zones containing Schwann cells and CAFs in close proximity surrounded by vasculature and skeletal muscle. Endo_fibr, Endoneurial fibroblasts; Epi_fibr, Epineurial fibroblasts; HB, Hemoglobin; NM-SC, Non-myelinating Schwann cells; SC, Schwann cells; VE, Vascular endothelium