Fig. 2: The early tumour niche is formed by a PDGFRα^low fibroblast population.

a, Representative confocal image of a nascent Niche+ tumour 10 days after DEN withdrawal. The side view shows that the niche is composed of lamina propria (Lp), not submucosae (Sb), fibroblasts. Mm, muscularis mucosae; Ep, epithelium. Dashed lines show the layers. The white arrowhead points to the nascent tumour niche arising from lamina propria. Blue, DAPI; red, KRT6A; grey, PDGFRα. Scale bar, 25 µm. b, Number of stromal cells in tumour-free DEN tissue, Niche− and Niche+ tumours per unit of surface area, 10 days after DEN withdrawal; n = 27 Niche−, n = 22 Niche+, n = 15 (DEN) areas, from 3 mice; dots represent each area; PDGFRα⁺ fibroblasts, CD45⁺ immune cells and CD31⁺ endothelial cells are shown. Data are expressed as mean ± s.e.m. Statistical significance was assessed by one way Welch’s analysis of variance (ANOVA) with multiple comparisons. c, 3D-rendered confocal side views of Niche− and Niche+ tumours 10 days after DEN withdrawal; green, CD45; orange, CD31 (absent); red, KRT6A; grey, PDGFRα. Dashed lines show the basal membrane. Scale bar, 10 μm. Image settings were adjusted to the upper stromal layer. d, Experimental protocol for fibroblast lineage tracing: Col1a2^CreER and R26^{FlConfetti/wt} mice received a dose of tamoxifen (TAM) followed by DEN treatment. Samples were collected 6 months after DEN treatment. e, Representative top-down (top) and side views (bottom) of control and tumour tissue from d, Grey, PDGFRα; yellow and red, lineage-traced Confetti⁺ cells. Scale bars, 50 µm. Dashed lines separate stromal compartments. Control, n = 3 mice; DEN, n = 4 mice. f, A single channel from e shows a marked difference in PDGFRα expression across the two stromal compartments, both in control and tumour samples; lamina propria, PDGFRα^low (underlying epithelium); submucosae, PDGFRα^high (deeper stromal layer). The illustration in d was created in BioRender; Alcolea, M. https://BioRender.com/hwbs32m (2026).

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