TY - JOUR
T1 - ARTS mediates apoptosis and regeneration of the intestinal stem cell niche
AU - Koren, Elle
AU - Yosefzon, Yahav
AU - Ankawa, Roi
AU - Soteriou, Despina
AU - Jacob, Avi
AU - Nevelsky, Alexander
AU - Ben-Yosef, Rahamim
AU - Bar-Sela, Gil
AU - Fuchs, Yaron
N1 - Publisher Copyright:
© 2018, The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85056002029&partnerID=8YFLogxK
U2 - 10.1038/s41467-018-06941-4
DO - 10.1038/s41467-018-06941-4
M3 - Article
C2 - 30389919
AN - SCOPUS:85056002029
SN - 2041-1723
VL - 9
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 4582
ER -
