| First Author | Marruecos L | Year | 2020 |
| Journal | EMBO Rep | Volume | 21 |
| Issue | 6 | Pages | e49708 |
| PubMed ID | 32270911 | Mgi Jnum | J:292648 |
| Mgi Id | MGI:6448777 | Doi | 10.15252/embr.201949708 |
| Citation | Marruecos L, et al. (2020) IkappaBalpha deficiency imposes a fetal phenotype to intestinal stem cells. EMBO Rep 21(6):e49708 |
| abstractText | 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 IkappaBalpha, the main regulator of NF-kappaB, exerts alternative nuclear functions as cytokine sensor in a subset of PRC2-regulated genes. Here, we show that nuclear IkappaBalpha is present in the ISC compartment. Mice deficient for IkappaBalpha show altered intestinal cell differentiation with persistence of a fetal-like ISC phenotype, associated with aberrant PRC2 activity at specific loci. Moreover, IkappaBalpha-deficient intestinal cells produce morphologically aberrant organoids carrying a PRC2-dependent fetal-like transcriptional signature. DSS treatment, which induces acute damage in the colonic epithelium of mice, results in a temporary loss of nuclear P-IkappaBalpha and its subsequent accumulation in early CD44-positive regenerating areas. Importantly, IkappaBalpha-deficient mice show higher resistance to damage, likely due to the persistent fetal-like ISC phenotype. These results highlight intestinal IkappaBalpha as a chromatin sensor of inflammation in the ISC compartment. |
