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GLI1-expressing mesenchymal cells form the essential Wnt-secreting niche for colon stem cells

Author

Listed:
  • Bahar Degirmenci

    (Institute of Molecular Life Sciences, University of Zurich)

  • Tomas Valenta

    (Institute of Molecular Life Sciences, University of Zurich
    Institute of Molecular Genetics of the ASCR)

  • Slavica Dimitrieva

    (Functional Genomics Center Zurich, ETH/University of Zurich)

  • George Hausmann

    (Institute of Molecular Life Sciences, University of Zurich)

  • Konrad Basler

    (Institute of Molecular Life Sciences, University of Zurich)

Abstract

Wnt–β-catenin signalling plays a pivotal role in the homeostasis of the intestinal epithelium by promoting stem cell renewal1,2. In the small intestine, epithelial Paneth cells secrete Wnt ligands and thus adopt the function of the stem cell niche to maintain epithelial homeostasis3,4. It is unclear which cells comprise the stem cell niche in the colon. Here we show that subepithelial mesenchymal GLI1-expressing cells form this essential niche. Blocking Wnt secretion from GLI1-expressing cells prevents colonic stem cell renewal in mice: the stem cells are lost and, as a consequence, the integrity of the colonic epithelium is corrupted, leading to death. GLI1-expressing cells also play an important role in the maintenance of the small intestine, where they serve as a reserve Wnt source that becomes critical when Wnt secretion from epithelial cells is prevented. Our data suggest a mechanism by which the stem cell niche is adjusted to meet the needs of the intestine via adaptive changes in the number of mesenchymal GLI1-expressing cells.

Suggested Citation

  • Bahar Degirmenci & Tomas Valenta & Slavica Dimitrieva & George Hausmann & Konrad Basler, 2018. "GLI1-expressing mesenchymal cells form the essential Wnt-secreting niche for colon stem cells," Nature, Nature, vol. 558(7710), pages 449-453, June.
    • Handle: RePEc:nat:nature:v:558:y:2018:i:7710:d:10.1038_s41586-018-0190-3
    DOI: 10.1038/s41586-018-0190-3
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    Cited by:

    1. Jeremiah Bernier-Latmani & Cristina Mauri & Rachel Marcone & François Renevey & Stephan Durot & Liqun He & Michael Vanlandewijck & Catherine Maclachlan & Suzel Davanture & Nicola Zamboni & Graham W. K, 2022. "ADAMTS18+ villus tip telocytes maintain a polarized VEGFA signaling domain and fenestrations in nutrient-absorbing intestinal blood vessels," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Ryan J. Smith & Minggao Liang & Adrian Kwan Ho Loe & Theodora Yung & Ji-Eun Kim & Matthew Hudson & Michael D. Wilson & Tae-Hee Kim, 2023. "Epigenetic control of cellular crosstalk defines gastrointestinal organ fate and function," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    3. Elisa Manieri & Guodong Tie & Ermanno Malagola & Davide Seruggia & Shariq Madha & Adrianna Maglieri & Kun Huang & Yuko Fujiwara & Kevin Zhang & Stuart H. Orkin & Timothy C. Wang & Ruiyang He & Neil Mc, 2023. "Role of PDGFRA+ cells and a CD55+ PDGFRALo fraction in the gastric mesenchymal niche," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    4. Martti Maimets & Marianne Terndrup Pedersen & Jordi Guiu & Jes Dreier & Malte Thodberg & Yasuko Antoku & Pawel J. Schweiger & Leonor Rib & Raul Bardini Bressan & Yi Miao & K. Christopher Garcia & Albi, 2022. "Mesenchymal-epithelial crosstalk shapes intestinal regionalisation via Wnt and Shh signalling," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    5. Liang Yang & Zifeng Ruan & Xiaobing Lin & Hao Wang & Yanmin Xin & Haite Tang & Zhijuan Hu & Yunhao Zhou & Yi Wu & Junwei Wang & Dajiang Qin & Gang Lu & Kerry M. Loomes & Wai-Yee Chan & Xingguo Liu, 2024. "NAD+ dependent UPRmt activation underlies intestinal aging caused by mitochondrial DNA mutations," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    6. Mara Martín-Alonso & Sharif Iqbal & Pia M. Vornewald & Håvard T. Lindholm & Mirjam J. Damen & Fernando Martínez & Sigrid Hoel & Alberto Díez-Sánchez & Maarten Altelaar & Pekka Katajisto & Alicia G. Ar, 2021. "Smooth muscle-specific MMP17 (MT4-MMP) regulates the intestinal stem cell niche and regeneration after damage," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    7. Simone Isling Pærregaard & Line Wulff & Sophie Schussek & Kristoffer Niss & Urs Mörbe & Johan Jendholm & Kerstin Wendland & Anna T. Andrusaite & Kevin F. Brulois & Robert J. B. Nibbs & Katarzyna Sitni, 2023. "The small and large intestine contain related mesenchymal subsets that derive from embryonic Gli1+ precursors," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    8. Urban Lendahl & Lars Muhl & Christer Betsholtz, 2022. "Identification, discrimination and heterogeneity of fibroblasts," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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