Fig. 1: LXR activation in vivo promotes intestinal regeneration in response to damage.

a, Haematoxylin and eosin (H&E) staining and Abca1 transcript levels in 0 and 3 d.p.i. SI Swiss rolls. The Abca1 levels in the tissue (left) and quantification per spot (right) are shown. ST, spatial transcriptomics. b, RNA scope analysis of Abca1 and Lgr5 transcripts at 0 and 3 d.p.i. in the SI. The white arrows in magnified crypts indicate Abca1 transcripts. Scale bars, 25 μm. c,d, Abca1 expression in SI crypts at 0, 1 and 3 d.p.i. (c) and ileal crypts of DSS-treated WT mice (d). e, H&E images and Visiopharm artificial intelligence deconvolution showing crypt (red) and villi (yellow) (left). Quantification of the normalized crypt area and crypt:villus area (right) of distal SI from standard (STD)-diet-fed and GW3965-fed WT mice at 5 d.p.i. is shown. Scale bars, 2 mm (left) and 100 μm (right). f, H&E images of colon Swiss rolls and histopathological assessment after recovery (day 14 (d14)) from DSS treatment in WT mice fed with standard or GW3965 diet. Scale bars, 2 mm (left) and 500 μm (right). g, BrdU-stained images and quantification of the percentage of surviving crypts and BrdU⁺ cells per crypt in the distal SI at 5 d.p.i. Scale bars, 100 μm. h,i, Experimental schematic (left) and staining and quantification of BrdU⁺ cells per colonic crypt (right) (h) and colon length (i) at day 14 after DSS treatment. Scale bars, 200 μm (h). j, Schematic of the experiment (left). Representative ileal organoid (day 5) images with quantification of average buds per organoid and the percentage of organoids with the indicated number of buds. Scale bars, 200 μm. Data are representative of one (a,b), two (d–h) or three (c,i,j) independent experiments with 4–10 mice per condition (each dot is a biological replicate). For c–j, data are mean and s.e.m. P values were calculated using Wilcoxon tests (a), one-way analysis of variance (ANOVA) with Bonferroni’s test (c,d), unpaired two-tailed t-tests (e–j) and two-way ANOVA with Bonferroni’s test (de novo buds in j). The dashed lines denote crypts and villi in the same plane. The diagrams in h and j were adapted from ref. ¹⁹, CC-BY 4.0.

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