Fig. 4: LXR activation in vivo suppresses intestinal tumorigenesis.

a, Representative images and quantification of tumour numbers and size at day 70 of AOM–DSS-induced tumorigenesis in WT mice that were fed a standard or GW3965 diet. Scale bar, 1 cm. b, Representative images and quantification of tumour numbers and size at day 70 of AOM–DSS-induced tumorigenesis in Cyp27a1^−/− and littermate controls fed as indicated. c, Longitudinal bulk RNA-seq analysis of mouse colon from AOM–DSS WT mice fed with standard (S) or GW3965 diet. Clustered heatmap of DEGs for the diet or diet:time interactions (likelihood ratio test, false-discovery rate (FDR) < 0.05), divided into modules of similar gene behaviour (left). Mean-scaled log-fold-change (compared with day 0) of each gene module (m1–m9) for each timepoint/diet group and the top KEGG pathways significantly enriched (adjusted P < 0.05) (right). d, The scores of selected B cell and plasma cell clusters from quantitative deconvolution of scRNA-seq data⁴⁹ onto colon Swiss roll spatial transcriptomics from day 0 (standard diet), day 22 and day 43 (standard and GW3965 diet) AOM–DSS-treated mice. e, Representative images and quantification of B220 immunohistochemical staining of colons from AOM–DSS treated WT mice that were fed with standard or GW3965 diet at day 70. Scale bars, 2.5 mm. f,g, Schematic (f) and representative images and quantification of tumour numbers (log₂ normalized) and sizes (g) from AOM–DSS-treated WT mice fed on a standard or GW3965 diet and treated with repeated intraperitoneal injections of anti-CD19 and anti-CD8 antibodies or PBS as shown in the schematic. Data are representative of 2–4 (a,b,e,g) independent experiments with 4–13 mice per condition (each dot represents one biological replicate); one experiment with 3–4 mice per timepoint for bulk RNA-seq (c); one mouse per timepoint from one experiment for spatial transcriptomics (d). For a,b,e,g, data are mean ± s.e.m. Significance was assessed using two-tailed unpaired t-tests (a,e) or one-way ANOVA with fisher’s LSD (b) and Tukey’s (g) post hoc test. The dashed lines denote tumours. The diagram in f was adapted from ref. ¹⁹, CC-BY 4.0.

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