ARTS mediates apoptosis and regeneration of the intestinal stem cell niche.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30389919.
- Also identified by DOI 10.1038/s41467-018-06941-4 and PMC identifier 6214937.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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<sup>+</sup> and Paneth cells from undergoing apoptotic cell death. As a result, the Sept4/ARTS<sup>-/-</sup> crypt displays augmented proliferation and, in culture, generates massive cystic-like organoids due to enhanced Wnt/β-catenin signaling. Importantly, Sept4/ARTS<sup>-/-</sup> mice exhibit resistance against intestinal damage in a manner dependent upon Lgr5<sup>+</sup> SCs. Finally, we show that ARTS interacts with XIAP in intestinal crypt cells and that deletion of XIAP can abrogate Sept4/ARTS<sup>-/-</sup>-dependent phenotypes. Our results indicate that intestinal SCs utilize specific apoptotic proteins for their elimination, representing a unique target for regenerative medicine.
Medical subject headings
- Apoptosis
- Intestines
- Regeneration
- Septins
- Stem Cell Niche