Enteroendocrine and tuft cells support Lgr5 stem cells on Paneth cell depletion

Johan H. van Es, Kay Wiebrands, Carmen Lopez-Iglesias, Marc van de Wetering, Laura Zeinstra, Maaike van den Born, Jeroen Korving, Nobuo Sasaki, Peter J. Peters, Alexander van Oudenaarden, Hans Clevers*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Cycling intestinal Lgr5(+) stem cells are intermingled with their terminally differentiated Paneth cell daughters at crypt bottoms. Paneth cells provide multiple secreted (e.g., Wnt, EGF) as well as surface-bound (Notch ligand) niche signals. Here we show that ablation of Paneth cells in mice, using a diphtheria toxin receptor gene inserted into the P-lysozyme locus, does not affect the maintenance of Lgr5(+) stem cells. Flow cytometry, single-cell sequencing, and histological analysis showed that the ablated Paneth cells are replaced by enteroendocrine and tuft cells. As these cells physically occupy Paneth cell positions between Lgr5(+) stem cells, they serve as an alternative source of Notch signals, which are essential for Lgr5(+) stem cell maintenance. Our combined in vivo results underscore the adaptive flexibility of the intestine in maintaining normal tissue homeostasis.

Original languageEnglish
Pages (from-to)26599-26605
Number of pages7
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number52
DOIs
Publication statusPublished - 26 Dec 2019

Keywords

  • intestine
  • Paneth cells
  • stem cells
  • Notch
  • SECRETORY PRECURSORS
  • SMALL-INTESTINE
  • COLON
  • ABLATION
  • MARKER
  • GENE

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