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Review
. 2012 Jun 13;31(12):2685-96.
doi: 10.1038/emboj.2012.149. Epub 2012 May 22.

Adult mammalian stem cells: the role of Wnt, Lgr5 and R-spondins

Jurian Schuijers  1 , Hans Clevers
Affiliations
Review

Adult mammalian stem cells: the role of Wnt, Lgr5 and R-spondins

Jurian Schuijers et al. EMBO J. .

Abstract

After its discovery as oncogen and morphogen, studies on Wnt focused initially on its role in animal development. With the finding that the colorectal tumour suppressor gene APC is a negative regulator of the Wnt pathway in (colorectal) cancer, attention gradually shifted to the study of the role of Wnt signalling in the adult. The first indication that adult Wnt signalling controls stem cells came from a Tcf4 knockout experiment: mutant mice failed to build crypt stem cell compartments. This observation was followed by similar findings in multiple other tissues. Recent studies have indicated that Wnt agonists of the R-spondin family provide potent growth stimuli for crypts in vivo and in vitro. Independently, Lgr5 was found as an exquisite marker for these crypt stem cells. The story has come full circle with the finding that the stem cell marker Lgr5 constitutes the receptor for R-spondins and occurs in complex with Frizzled/Lrp.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
Structure of the intestinal epithelium. (A) The inner surface epithelium of the small intestine is folded into large numbers of villi. (B, C) In-between the villi are the crypts of lieberkühn. (D) Electron microscopy image of an intestinal crypt with slender crypt base columnar (CBC) cells residing in-between granulated Paneth cells (P). Reproduced with the kind permission of Prof Dr Wim A Buurman (Maastricht University). (E) Schematic representation of a single small intestinal crypt for reference.
Figure 2
Figure 2
Stem cell compartment of the small intestine and its cell types. Lgr5+ CBC stem cells reside in the bottom of the crypt and push their progeny up the villus.
Figure 3
Figure 3
Cultured Lgr5+ stem cells form organoids. (A) Schematic representation of an organoid with the lumen corresponding to the intestinal lumen. (B) Organoid expressing GFP under the Lgr5 promoter.
Figure 4
Figure 4
Stomach and hair follicle. (A) The gastric glands of the stomach are subdivided in the pit, isthmus and gland. Lgr5+ cells reside at the bottom and regenerate the epithelium. (B) Multiple stem cell populations are responsible for homeostasis of the adult skin.
Figure 5
Figure 5
Lgrs in the Wnt pathway. Protein interaction data show that the Lgrs are in direct contact with Lrp5/6 and Frizzelds, placing them in the heart of the receptor complex for Wnt ligands.
See this image and copyright information in PMC

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