ARTS mediates apoptosis and regeneration of the intestinal stem cell niche

• DOI: 10.1038/s41467-018-06941-4
• Publication Date: 2018-10-29T10:32:08Z
• Authors: Elle Koren; Yahav Yosefzon; Roi Ankawa; Despina Soteriou; Avi Jacob; Alexander Nevelsky; Rahamim Ben-Yosef; Gil Bar-Sela; Yaron Fuchs
• Keywords: LGR5; XIAP; Regenerative Medicine

Stem cells (SCs) play a pivotal role in fueling homeostasis and regeneration. While much focus has been given to self-renewal differentiation pathways regulating SC fate, little is known regarding the specific mechanisms utilized for their elimination. Here, we report that pro-apoptotic protein ARTS (a Septin4 isoform) highly expressed comprising intestinal niche its deletion protects Lgr5+ Paneth from undergoing apoptotic cell death. As result, Sept4/ARTS-/- crypt displays augmented proliferation and, culture, generates massive cystic-like organoids due enhanced Wnt/β-catenin signaling. Importantly, mice exhibit resistance against damage manner dependent upon SCs. Finally, show interacts with XIAP of can abrogate Sept4/ARTS-/--dependent phenotypes. Our results indicate SCs utilize proteins elimination, representing unique target regenerative medicine.