Fig. 8: p57⁺ EE lineage cells in intestinal adenoma manifest homeostatic stem cell activity in the context of constitutively activated spatiotemporal reprogramming.

a Representative immunofluorescence staining of p57 in intestinal adenoma of an Apc^Δ716 mouse. b Representative FACS plot for adenoma cells from Apc^Δ716/p57-DTR-Venus mice and gating strategy for isolation of p57⁺ cells. c RT-qPCR analysis of relative mRNA abundance for EE cell markers (Chga and Chgb) and LRC markers (Peg3 and Rfx6) in FACS-sorted p57-Venus⁺ and total adenoma cells as in b. Data are means + SEM (n = 3 mice). *P < 0.05, ****P < 0.001 (two-tailed Student’s t test). d Schematic representation of labeling or lineage tracing for p57⁺ cells in intestinal adenoma of mice harboring the Apc^Δ716 allele. e Confocal immunofluorescence analysis of Ki67 expression and tdTomato-labeled p57⁺ cells in intestinal adenoma at 24 h after tamoxifen injection in an Apc^Δ716/p57-CreER^T2/CAG-LSL-tdTomato mouse. The boxed regions of the left panel are shown at higher magnification on the right. No Ki67⁺tdTomato⁺ cells were apparent. f Representative image (tdTomato fluorescence and differential interference contrast) of a cleared whole-mount intestinal adenoma preparation from an Apc^Δ716/p57-CreER^T2/CAG-LSL-tdTomato mouse at 1 month after tamoxifen injection. The dashed line indicates the tumor outline. g, h Confocal immunofluorescence images for the tdTomato-labeled p57⁺ cell-derived lineage stained for Ki67 (g) or for Lgr5-GFP (h) in intestinal adenoma of Apc^Δ716/p57-CreER^T2/CAG-LSL-tdTomato or Apc^Δ716/p57-CreER^T2/CAG-LSL-tdTomato/Lgr5-DTR-EGFP mice, respectively, at 1 month after tamoxifen injection. i–l Representative immunofluorescence staining of the fetal intestinal marker Sca1 (i) and the adult stomach markers Tff2 (j), Pgc (k), and Gif (l) in intestinal adenoma of Apc^Δ716 mice. Scale bars: 50 μm (a, e, g–l) or 200 μm (f). Source data are provided as a Source Data file.