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

doi:10.1073/pnas.1801888117

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 journal › Article › Academic › peer-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 language	English
Pages (from-to)	26599-26605
Number of pages	7
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	116
Issue number	52
DOIs	https://doi.org/10.1073/pnas.1801888117
Publication status	Published - 26 Dec 2019

Keywords

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

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10.1073/pnas.1801888117

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Cite this

van Es, J. H., Wiebrands, K., Lopez-Iglesias, C., de Wetering, M. V., 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, 116(52), 26599-26605. https://doi.org/10.1073/pnas.1801888117

@article{2774c497ae9c4a0388e21483ff462dea,

title = "Enteroendocrine and tuft cells support Lgr5 stem cells on Paneth cell depletion",

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.",

keywords = "intestine, Paneth cells, stem cells, Notch, SECRETORY PRECURSORS, SMALL-INTESTINE, COLON, ABLATION, MARKER, GENE",

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

year = "2019",

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doi = "10.1073/pnas.1801888117",

language = "English",

volume = "116",

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journal = "Proceedings of the National Academy of Sciences of the United States of America",

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publisher = "National Academy of Sciences",

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van Es, JH, Wiebrands, K, Lopez-Iglesias, C, de Wetering, MV, Zeinstra, L, van den Born, M, Korving, J, Sasaki, N, Peters, PJ, 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

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T1 - Enteroendocrine and tuft cells support Lgr5 stem cells on Paneth cell depletion

AU - van Es, Johan H.

AU - Wiebrands, Kay

AU - Lopez-Iglesias, Carmen

AU - de Wetering, Marc van

AU - Zeinstra, Laura

AU - van den Born, Maaike

AU - Korving, Jeroen

AU - Sasaki, Nobuo

AU - Peters, Peter J.

AU - van Oudenaarden, Alexander

AU - Clevers, Hans

PY - 2019/12/26

Y1 - 2019/12/26

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AB - 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.

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KW - COLON

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KW - GENE

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