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R-spondin 3 promotes stem cell recovery and epithelial regeneration in the colon

Author

Listed:
  • Christine Harnack

    (Charité University Medicine
    Max Planck Institute for Infection Biology)

  • Hilmar Berger

    (Max Planck Institute for Infection Biology)

  • Agne Antanaviciute

    (University of Oxford)

  • Ramon Vidal

    (Max Delbrück Center)

  • Sascha Sauer

    (Max Delbrück Center
    Berlin Institute of Health)

  • Alison Simmons

    (University of Oxford)

  • Thomas F. Meyer

    (Max Planck Institute for Infection Biology)

  • Michael Sigal

    (Charité University Medicine
    Max Planck Institute for Infection Biology
    Berlin Institute of Health)

Abstract

The colonic epithelial turnover is driven by crypt-base stem cells that express the R-spondin receptor Lgr5. Signals that regulate epithelial regeneration upon stem cell injury are largely unknown. Here, we explore the dynamics of Wnt signaling in the colon. We identify two populations of cells with active Wnt signaling: highly proliferative Lgr5+/Axin2+ cells, as well as secretory Lgr5−/Axin2+ cells. Upon Lgr5+ cell depletion, these cells are recruited to contribute to crypt regeneration. Chemical injury induced by DSS leads to a loss of both Lgr5+ cells and Axin2+ cells and epithelial regeneration is driven by Axin2− cells, including differentiated Krt20+ surface enterocytes. Regeneration requires stromal Rspo3, which is present at increased levels upon injury and reprograms Lgr5− but Lgr4+ differentiated cells. In contrast, depletion of stromal Rspo3 impairs crypt regeneration, even upon mild injury. We demonstrate that Rspo3 is essential for epithelial repair via induction of Wnt signaling in differentiated cells.

Suggested Citation

  • Christine Harnack & Hilmar Berger & Agne Antanaviciute & Ramon Vidal & Sascha Sauer & Alison Simmons & Thomas F. Meyer & Michael Sigal, 2019. "R-spondin 3 promotes stem cell recovery and epithelial regeneration in the colon," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12349-5
    DOI: 10.1038/s41467-019-12349-5
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    Cited by:

    1. Marta Kapalczynska & Manqiang Lin & Jeroen Maertzdorf & Julian Heuberger & Stefanie Muellerke & Xiangsheng Zuo & Ramon Vidal & Imad Shureiqi & Anne-Sophie Fischer & Sascha Sauer & Hilmar Berger & Evel, 2022. "BMP feed-forward loop promotes terminal differentiation in gastric glands and is interrupted by H. pylori-driven inflammation," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    2. Manqiang Lin & Kimberly Hartl & Julian Heuberger & Giulia Beccaceci & Hilmar Berger & Hao Li & Lichao Liu & Stefanie Müllerke & Thomas Conrad & Felix Heymann & Andrew Woehler & Frank Tacke & Nikolaus , 2023. "Establishment of gastrointestinal assembloids to study the interplay between epithelial crypts and their mesenchymal niche," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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