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| Item Type: | Article |
|---|---|
| Title: | ARTS mediates apoptosis and regeneration of the intestinal stem cell niche |
| Creators Name: | Koren, E. and Yosefzon, Y. and Ankawa, R. and Soteriou, D. and Jacob, A. and Nevelsky, A. and Ben-Yosef, R. and Bar-Sela, G. and Fuchs, Y. |
| 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(+) 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/β-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. |
| Keywords: | Apoptosis, Cell Proliferation, Cytoprotection, Gene Deletion, Inbred C57BL Mice, Intestines, Regeneration, Septins, Stem Cell Niche, Wnt Signaling Pathway, Wounds and Injuries, X-Linked Inhibitor of Apoptosis Protein, Animals, Mice |
| Source: | Nature Communications |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Volume: | 9 |
| Number: | 1 |
| Page Range: | 4582 |
| Date: | 2 November 2018 |
| Official Publication: | https://doi.org/10.1038/s41467-018-06941-4 |
| PubMed: | View item in PubMed |
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