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

By Toshiro Sato, Johan H. van Es, Hugo J. G. Snippert, D. Stange, R. Vries, Maaike van den Born, Nick Barker, N. Shroyer, M. van de Wetering, Hans Clevers. Nature, 2010

2,475 citations recorded by the source corpus.

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-α, 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.

Subfields: Genetics, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/c2d04ae6b6fd04930a0a9b3b345ed62aae9f667d

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Citations in the corpus

Wnt/β-catenin signaling and disease. (2012, neutral): “Applications of the drug have been limited to cell culture experiments and have demonstrated Wnt dependency of stem cells in self-renewal assays (Sato et al., 2010; Ten Berge et al., 2011).”
Unlimited in vitro expansion of adult bi-potent pancreas progenitors through the Lgr5/R-spondin axis (2013, neutral): “The colony formation efﬁciency was B 16%, similar to the colony formation of Lgr5 cells of small intestine and stomach (Barker et al , 2010; Sato et al , 2011) (Figure 4C).”
R-spondins function as ligands of the orphan receptors LGR4 and LGR5 to regulate Wnt/β-catenin signaling (2011, background): “Importantly, RSPO1 was found to be expressed in the Paneth cells of the crypt, which surround and form the niche for the LGR5 stem cells (32, 33).”
Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis (2011, background): “Furthermore, other Paneth cell products function as vital trophic factors for the stem cells of the small intestin”
Single-cell dissection of transcriptional heterogeneity in human colon tumors (2011, background): “This phenomenon is best exemplified in the case of the mouse small intestine, where growth and expansion of LGR5 + progenitor cells is dramatically enhanced by the presence of bystander epithelial feeder cell”
Organogenesis in a dish: Modeling development and disease using organoid technologies (2014, methodology): “Indeed, intestinal organoids have already been used to examine the role of the crypt niche in stem cell self-renewal and differentiation (79, 80).”
The intestinal stem cell markers Bmi1 and Lgr5 identify two functionally distinct populations (2011, background): “Single Lgr5-eGFP ISCs can generate in vitro spheroids in clonogenic culture without requiring a mesenchymal niche (19, 20).”
Plant exosome like nanovesicles: Emerging therapeutics and drug delivery nanoplatforms. (2020, background): “In addition, these findings also set the precedent for future implications of grapederived ELNVs for inducing the proliferation of Lgr5 stem cells in other ailments.(113) Moreover, ginger-derived ELNVs exhibited the role in curtailing the expression of the secreted protein hemopexin and also influen”