| First Author | Koren E | Year | 2018 |
| Journal | Nat Commun | Volume | 9 |
| Issue | 1 | Pages | 4582 |
| PubMed ID | 30389919 | Mgi Jnum | J:269496 |
| Mgi Id | MGI:6268242 | Doi | 10.1038/s41467-018-06941-4 |
| Citation | Koren E, et al. (2018) ARTS mediates apoptosis and regeneration of the intestinal stem cell niche. Nat Commun 9(1):4582 |
| abstractText | Stem cells (SCs) play a pivotal role in fueling homeostasis and regeneration. While much focus has been given to self-renewal and differentiation pathways regulating SC fate, little is known regarding the specific mechanisms utilized for their elimination. Here, we report that the pro-apoptotic protein ARTS (a Septin4 isoform) is highly expressed in cells comprising the intestinal SC niche and that its deletion protects Lgr5(+) and Paneth cells from undergoing apoptotic cell death. As a result, the Sept4/ARTS(-/-) crypt displays augmented proliferation and, in culture, generates massive cystic-like organoids due to enhanced Wnt/beta-catenin signaling. Importantly, Sept4/ARTS(-/-) mice exhibit resistance against intestinal damage in a manner dependent upon Lgr5(+) SCs. Finally, we show that ARTS interacts with XIAP in intestinal crypt cells and that deletion of XIAP can abrogate Sept4/ARTS(-/-)-dependent phenotypes. Our results indicate that intestinal SCs utilize specific apoptotic proteins for their elimination, representing a unique target for regenerative medicine. |
