Extended Data Fig. 1: LXR activation promotes intestinal regeneration without affecting tissue damage.
From: Liver X receptor unlinks intestinal regeneration and tumorigenesis
(a) Venn diagram showing differentially expressed genes (DEG) overlap between regenerative and steady state colonic tissue and small intestine (SI) crypts following DSS-induced colitis and irradiation, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis from shared differentially expressed genes (DEGs) between colon and SI. d&a: digestion and absorption. (b) Scheme of the experimental procedures shown in Extended Data Figs. 1–3 and Fig. 1. Briefly, WT mice were fed with standard (STD) or GW3965-containing diet for 10 days and then subjected to 10 Gy total body irradiation (TBI, i.e., damage) and allowed to heal (for 1, 3 or 5 days) while still on modified diet. Alternatively, mice were fed STD or GW3965 diet and simultaneously administered DSS in drinking water for 7 days (i.e., damage) followed by 2–7 days of regular water (i.e., healing). As a readout for mucosal healing the intestinal tissue was harvested for histology, blind clinical scoring, spatial transcriptomics and/or organoid culture. (c) Abca1 and Abcg1 expression by qPCR from SI crypts of mice at 3 days post irradiation (3dpi) or from colonic tissue of mice at day 14 of DSS-induced colitis. Datasets for irradiation are normalized to crypts from 0dpi. (d-e) Cumulative (d) and stratified (e) histological score of colonic tissue at day14 after DSS treatment of mice fed STD or GW3965 diet. (f) Representative images (1dpi) and quantification of cleaved caspase 3+ (cCASP3+) cells/crypt in the distal SI at 0, 1 and 3 dpi. (g) Olfm4 expression by qPCR in SI crypt at 0, 1 and 3 dpi from STD or GW3965 diet fed mice. In panels c, e-g each dot represents one mouse, and the data are representative of two (d-f) or three (c and g) independent experiments. Data are shown as bar plots with mean ± s.e.m. in (c-g). Significance was assessed by unpaired two-sided t test between diet groups (c, e-g). Part of the schematic in panel b was drawn using BioRender.com.
