Extended Data Fig. 10: Mutant clones drive niche stromal remodelling.
From: Tracing oncogene-driven remodelling of the intestinal stem cell niche
a, Heat map showing marker gene expression for STC2 among mesenchymal cells. Colour bar, averaged Z-scores of log2-transformed normalized UMIs over all cells within a cell type in Confetti mice. b, c, Representative multiplexed in situ hybridization images (b) and quantification (c) of Sfrp2 in Grem1+ cells on small intestine sections from Villin-CreERT2;R26R-Confetti or Red2Onco mice 2 w after tamoxifen administration. Arrowheads, fixed mutant crypts; grey dashed outlines indicate crypts; arrows, Grem1+ STC2 cells. d, Heat map showing expression of marker genes and secreted factors in STC1, 2 from Red2Onco and Confetti mice. Colour bar, averaged Z-scores of log2-transformed normalized UMIs over all cells within a cell type and condition. e, Projection of Pdgfra expression (middle) onto UMAP from Fig. 3f (left) for comparison. Projection of Cd81 expression onto Pdgfralo cell clusters (STC1, 2) (right). Colour bar, log2-transformed normalized UMIs. f, Sorting strategy to isolate STC2 from intestinal mesenchymal cells by FACS. R1, non-immune cells (CD45−); R2, mesenchymal cells (EPCAM−); R3, PDGFRAlo population. g, qPCR of STC2 markers (Cd81, Grem1), STC1 marker (Frzb) and secreted WNT modulators (Rspo3, Sfrp2, Sfrp4) using sorted CD45−EPCAM−PDGFRAloCD81− cells (STC1) or CD45−EPCAM−PDGFRAloCD81+ cells (STC2) from Villin-CreERT2;R26R-Confetti or Red2Onco mice 2 w after tamoxifen administration. h, qPCR of telocyte markers (Pdgfra, Foxl1) using sorted STC1, 2 and PDGFRAhi telocytes. *P < 0.05, **P < 0.01, ***P < 0.0001; one-way ANOVA with Games-Howell’s multiple comparisons test (c) and unpaired two-tailed t-test (g, h). Data are mean ± s.d. (c, g) or mean ± s.e.m. (h). For exact P values, see Source Data. Scale bars, 25 μm (b).
