GSE131185
I?Ba deficiency imposes a fetal phenotype to intestinal stem cells [ChIP-seq]
The intestinal epithelium is a paradigm of adult tissue in constant regeneration that is supported by intestinal stem cells (ISCs). The mechanisms regulating ISC homeostasis after injury are poorly understood.  We previously demonstrated that I?Ba, not only controls NF-?B activation, but also exerts nuclear functions as cytokine sensor in a subset of PRC2-regulated genes. We now uncover nuclear phosphorylated I?Ba (P-I?Ba) in the ISC compartment where it binds highly histone methylated genomic regions. Mice deficient for I?Ba show aberrant distribution of H3K27me3 mark, and altered intestinal differentiation with persistence of a fetal-like ISC signature. In vitro, I?Ba deficient intestinal cells produced morphologically aberrant organoids carrying a PRC2, Notch and IFN-dependent fetal-like transcriptional signature. Induction of the fetal-like phenotype by DSS treatment is associated with loss of nuclear P-I?Ba in the damaged colonic epithelium and it subsequent accumulation in early CD44 positive regenerating areas. Importantly, I?Ba deficient animals showed higher resistance to damage, likely due to persistent fetal-like phenotype. These results point out intestinal I?Ba as chromatin sensor of inflammation in the ISC compartment. Overall design: 16 samples analyzed, plus two different inputs