Figure 13.

SZN-1326-p predominately impacted the epithelium by promoting expression of Wnt target and cell cycle genes with a concomitant reduction in inflammatory pathway expression. (A) The number of significantly enriched intestinal epithelial organoid Wnt target genes in the indicated colon tissue layers or lineages. (B) Heatmap of canonical cell cycle gene expression in the epithelium displaying average Z scores for the genes. (C) Gene expression dot plot of canonical cell cycle genes in the epithelium across the 6 different experimental conditions. (D) RT-qPCR of bulk colon samples in the DSS model at the day 5 time point except Gpx2, which is from day 6. Unpaired, 2-tailed t tests were applied with the Holm multiple comparisons correction: ∗P < .05, ∗∗P < .01, ∗∗∗P = .001. (F) Selected top pathways reduced (derived from GSEA) in the epithelium after SZN-1326-p treatment relative to the anti-GFP treatment in the DSS model at 48 hours (day 6). (G) Expression of S100A9 and CD45 at day 10 (6 days after treatment); 2 example images each from the indicated treatment condition. Scale bar = 200 μm.