Enteroendocrine and tuft cells support Lgr5 stem cells on Paneth cell depletion
Publication date
2019-12-26
Authors
Van Es, Johan H.
Wiebrands, Kay
López-Iglesias, Carmen
van de Wetering, Marc
Zeinstra, Laura
Van Den Born, Maaike
Korving, Jeroen
Sasaki, Nobuo
Peters, Peter J.
van Oudenaarden, Alexander
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Supervisors
Document Type
Article
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Abstract
Cycling intestinal Lgr5+ stem cells are intermingled with their terminally differentiated Paneth cell daughters at crypt bottoms. Paneth cells providemultiple secreted (e.g.,Wnt, EGF) aswell as surfacebound (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.
Keywords
Intestine, Notch, Paneth cells, Stem cells, Taverne, General
Citation
Van Es, J H, Wiebrands, K, López-Iglesias, C, Van De Wetering, M, Zeinstra, L, Van Den Born, M, Korving, J, Sasaki, N, Peters, P J, Van Oudenaarden, A & Clevers, H 2019, 'Enteroendocrine and tuft cells support Lgr5 stem cells on Paneth cell depletion', Proceedings of the National Academy of Sciences of the United States of America, vol. 116, no. 52, pp. 26599-26605. https://doi.org/10.1073/pnas.1801888117