Epithelial XBP1 coordinates TP53-driven DNA damage responses and suppression of intestinal carcinogenesis. Epithelial XBP1 coordinates TP53-driven DNA damage responses and suppression of intestinal carcinogenesis

We assessed the impact of intestinal epithelial XBP1 in coordinating epithelial DNA damage responses. As our data revealed that low XBP1 activity in the context of chronic DNA damage is associated with both reduced p53 pathway activity and formation of tumors with metastaic potential in-vivo, we performed RNA sequencing of intestinal organoids (H2b/Xbp1fl/fl, H2bΔIEC, H2b/Xbp1ΔIEC, H2b/p53∆IEC) to identify a transcriptional program downstream of p53 that drives the tumorigenic in-vivo phenotype. Overall design: Examination of Differentially Expressed Genes between small intestinal organoids derived from healthy tissue of 8-12 weeks old mice (n = 3) of indicated genotypes.