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ARTS mediates apoptosis and regeneration of the intestinal stem cell niche

Author

Listed:
  • Elle Koren

    (Technion Israel Institute of Technology
    Technion Israel Institute of Technology
    Technion Israel Institute of Technology)

  • Yahav Yosefzon

    (Technion Israel Institute of Technology
    Technion Israel Institute of Technology
    Technion Israel Institute of Technology)

  • Roi Ankawa

    (Technion Israel Institute of Technology
    Technion Israel Institute of Technology
    Technion Israel Institute of Technology)

  • Despina Soteriou

    (Technion Israel Institute of Technology
    Technion Israel Institute of Technology
    Technion Israel Institute of Technology)

  • Avi Jacob

    (Bar-Ilan University)

  • Alexander Nevelsky

    (Rambam Health Care Campus)

  • Rahamim Ben-Yosef

    (Rambam Health Care Campus)

  • Gil Bar-Sela

    (Rambam Health Care Campus)

  • Yaron Fuchs

    (Technion Israel Institute of Technology
    Technion Israel Institute of Technology
    Technion Israel Institute of Technology)

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.

Suggested Citation

  • Elle Koren & Yahav Yosefzon & Roi Ankawa & Despina Soteriou & Avi Jacob & Alexander Nevelsky & Rahamim Ben-Yosef & Gil Bar-Sela & Yaron Fuchs, 2018. "ARTS mediates apoptosis and regeneration of the intestinal stem cell niche," Nature Communications, Nature, vol. 9(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06941-4
    DOI: 10.1038/s41467-018-06941-4
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    Cited by:

    1. Marianna Yusupova & Roi Ankawa & Yahav Yosefzon & David Meiri & Ido Bachelet & Yaron Fuchs, 2023. "Apoptotic dysregulation mediates stem cell competition and tissue regeneration," Nature Communications, Nature, vol. 14(1), pages 1-20, December.

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