Extended Data Fig. 12: Apc mutation induces reduction of stem cells in neighbouring wild-type crypts.
From: Tracing oncogene-driven remodelling of the intestinal stem cell niche
a, b, Representative confocal images of small intestine from Villin-CreERT2; Apcf/f mice at 2 w after tamoxifen administration (a) and from ApcMin/+ mice at 12 weeks of age (b). Images are representative of two independent experiments. OLFM4 staining shows a reduced number of stem cells in wild-type crypts neighbouring mutant crypts. Grey dashed outlines, Apc mutant foci (Villin-CreERT2; Apcf/f) or polyps (ApcMin/+); white dashed outlines, crypt borders. Scale bars, 50 μm. c, Bright-field images of intestinal organoids after 7 days of culture in ENR medium. Images are representative of three independent experiments. Note that organoids from Villin-CreERT2; Apcf/f mice form spheroids in ENR medium. Scale bars, 500 μm. d, qPCR analysis of WNT target gene (Axin2) and secreted WNT inhibitory factors (Dkk2, Wif1 and Notum) following Apc deletion. Data are mean ± s.d. n = 3 independent experiments. *P < 0.05, **P < 0.01, ***P < 0.0001; unpaired two-tailed t-test. e, f, Representative multiplexed in situ hybridization images of Axin2 and Wif1 (e) and Lgr5 and Notum (f) on sections of small intestine from Villin-CreERT2; Apcf/f mice 2 w after tamoxifen administration. Images are representative of two independent experiments. Axin2 (e) and Lgr5 (f) staining shows a reduced number of stem cells in wild-type crypts neighbouring Apc mutant crypts. Grey dashed outlines, Apc mutant foci (Villin-CreERT2; Apcf/f); white dashed outlines, crypt borders. Scale bars, 50 μm.
