Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts

Toshiro Sato, Johan H. Van Es, Hugo J. Snippert, Daniel E. Stange, Robert G. Vries, Maaike Van Den Born, Nick Barker, Noah F. Shroyer, Marc Van De Wetering, Hans Clevers

Research output: Contribution to journalArticle

1197 Citations (Scopus)

Abstract

Homeostasis of self-renewing small intestinal crypts results from neutral competition between Lgr5 stem cells, which are small cycling cells located at crypt bottoms. Lgr5 stem cells are interspersed between terminally differentiated Paneth cells that are known to produce bactericidal products such as lysozyme and cryptdins/defensins. Single Lgr5-expressing stem cells can be cultured to form long-lived, self-organizing crypt-villus organoids in the absence of non-epithelial niche cells. Here we find a close physical association of Lgr5 stem cells with Paneth cells in mice, both in vivo and in vitro. CD24 + Paneth cells express EGF, TGF-γ ±, Wnt3 and the Notch ligand Dll4, all essential signals for stem-cell maintenance in culture. Co-culturing of sorted stem cells with Paneth cells markedly improves organoid formation. This Paneth cell requirement can be substituted by a pulse of exogenous Wnt. Genetic removal of Paneth cells in vivo results in the concomitant loss of Lgr5 stem cells. In colon crypts, CD24 + cells residing between Lgr5 stem cells may represent the Paneth cell equivalents. We conclude that Lgr5 stem cells compete for essential niche signals provided by a specialized daughter cell, the Paneth cell.

Original languageEnglish
Pages (from-to)415-418
Number of pages4
JournalNature
Volume469
Issue number7330
DOIs
Publication statusPublished - 2011 Jan 20
Externally publishedYes

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Paneth Cells
Stem Cell Niche
Stem Cells
Organoids
Defensins
Muramidase
Epidermal Growth Factor
Colon
Homeostasis
Maintenance
Ligands

ASJC Scopus subject areas

  • General

Cite this

Sato, T., Van Es, J. H., Snippert, H. J., Stange, D. E., Vries, R. G., Van Den Born, M., ... Clevers, H. (2011). Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature, 469(7330), 415-418. https://doi.org/10.1038/nature09637

Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. / Sato, Toshiro; Van Es, Johan H.; Snippert, Hugo J.; Stange, Daniel E.; Vries, Robert G.; Van Den Born, Maaike; Barker, Nick; Shroyer, Noah F.; Van De Wetering, Marc; Clevers, Hans.

In: Nature, Vol. 469, No. 7330, 20.01.2011, p. 415-418.

Research output: Contribution to journalArticle

Sato, T, Van Es, JH, Snippert, HJ, Stange, DE, Vries, RG, Van Den Born, M, Barker, N, Shroyer, NF, Van De Wetering, M & Clevers, H 2011, 'Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts', Nature, vol. 469, no. 7330, pp. 415-418. https://doi.org/10.1038/nature09637
Sato T, Van Es JH, Snippert HJ, Stange DE, Vries RG, Van Den Born M et al. Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature. 2011 Jan 20;469(7330):415-418. https://doi.org/10.1038/nature09637
Sato, Toshiro ; Van Es, Johan H. ; Snippert, Hugo J. ; Stange, Daniel E. ; Vries, Robert G. ; Van Den Born, Maaike ; Barker, Nick ; Shroyer, Noah F. ; Van De Wetering, Marc ; Clevers, Hans. / Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. In: Nature. 2011 ; Vol. 469, No. 7330. pp. 415-418.
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