Figure 12.

SZN-1326-p increased Wnt target and cell cycle gene expression and expanded the progenitors in the epithelium. (A) Volcano plots of gene expression differences between the SZN-1326-p treatment and the anti-GFP treatment in the DSS damage model: the x-axis represents log2 expression, and the y-axis represents the -log10 of the adjusted P value (FDR) from differential expression analysis. Genes that show greater than absolute log2-fold change of 1 and FDR <0.05 are indicated in blue (decreased) and red (increased) in the indicated lineage or tissue layer and time point. Any gene with an FDR lower than 10E-5 was floored at 10E-5. (B) Average Z-scores of Wnt target, cell cycle, and progenitor gene expression aggregated by experimental condition within the epithelial lineage. (C) Relevant Wnt target, cell cycle, and stem/progenitor gene expression; size and intensity represent the percentage of cells with detectable expression and expression level, respectively. (D) Selected top gene sets or pathways (from GSEA) enriched in the SZN-1326-p treatment relative to the anti-GFP treated DSS-injured epithelium. (E) Expression of the Wnt target genes, Axin2 and Rnf43, in the AltEnteroPCs. (F) Boxplots showing expression of the cell cycle genes, Ccnb1, Cdca8, Cdk1 and Rfc5, that were enriched in the TA2 cells upon SZN-1326-p treatment. (G) RNA in situ hybridization of 2 Wnt target genes, Axin2 and Cdkn3 at day 5; nuclei labeled with DAPI. (H) Immunohistochemistry for the proliferative cell marker Ki67 at day 6; nuclei labeled with DAPI. Scale bars = 100 mm.