1. Leucine-Rich Repeat-Containing G-Protein-Coupled Receptors as Markers of Adult Stem Cells 
Nick Barker, Hans Clevers 
Gastroenterology 
Volume 138, Issue 5, Pages (May 2010)
DOI: /j.gastro
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2. Figure 1
A scheme of adult stem cell–driven tissue-renewal in organs such as intestine and stomach. (A) Stem cells concomitantly self-renew and generate rapidly dividing transit-amplifying daughter cells via asymmetric cell division. The transit-amplifying (ta) cells undergo several rounds of division before differentiating into the mature, functional cell types of the adult tissue. (B) Adult stem cells potentially can follow 3 modes of cell division: symmetric division to generate 2 stem cells, asymmetric division to generate 1 stem cell and 1 TA cell, or symmetric division to generate 2 TA cells.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2010 AGA Institute Terms and Conditions

3. Figure 2
Lgr5/GPR49 is an orphan, G-protein–coupled receptor related to the glycoprotein hormone receptors. (A) Predicted structure of Lgr5, comprising a large extracellular domain with multiple leucine-rich repeats that mediate ligand interaction, a 7TM domain, and an intracellular domain for signal transduction. (B) Phylogenetic relationship between Lgr5 and related family members. The ligands for Lgr4, Lgr5, and Lgr6 have not been identified.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2010 AGA Institute Terms and Conditions

4. Figure 3
An overview of the Lgr4/Lgr5/Lgr6 alleles currently used for exploring expression and function, in vivo. Top panel: domain structure of the Lgr proteins. (A) Lgr4 genetrap allele disrupts endogenous Lgr4 expression and marks Lgr4+ve cells in vivo via expression of the β-galactosidase and placental alkaline phosphatase reporter genes. (B) Lgr4 genetrap allele disrupts endogenous Lgr4 expression and marks Lgr4+ve cells in vivo via expression of the β-galactosidase reporter gene. (C) Inducible Lgr4 allele facilitates inducible Lgr4 deletion in tissues expressing Cre enzyme. (D) Lgr5-LacZ allele disrupts endogenous Lgr5 expression and marks Lgr5+ve cells in vivo via expression of the β-galactosidase reporter gene. (E) Lgr5-EGFP-ires-CreERT2 allele disrupts endogenous Lgr5 expression, marks Lgr5+ve cells in vivo via expression of the EGFP reporter gene, and facilitates lineage tracing in combination with inducible reporter mice. (F) Lgr6-LacZ allele disrupts endogenous Lgr6 expression and marks Lgr6+ve cells in vivo via expression of the β-galactosidase reporter gene.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2010 AGA Institute Terms and Conditions

5. Figure 4
In vivo lineage tracing reveals Lgr5+ve cells to be cycling intestinal stem cells. (A) Restricted expression of Lgr5 in the CBC cells at the crypt bottom. ta, transit-amplifying. (B) Lgr5-lacZ expression in the CBC cell population of Lgr5-lacZ knock-in mouse intestine. (C) Lgr5-EGFP expression in the CBC cell population of Lgr5-EGFP-ires-CreERT2 knock-in mouse intestine. (D) Upper panel: LacZ reporter gene activity initially is activated stochastically in Lgr5+ve cells at the crypt base after Tamoxifen administration (black arrows). Lower panel: at later time points, entirely Lgr5+ve cell-derived LacZ+ve crypt/villus units are visible throughout the intestine. Lgr5 cells continue generating this lacZ+ve epithelium over the entire lifetime of the mouse. (E) Generation of the major functional cell types of the intestine from the lgr5+ve CBC stem cell population.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2010 AGA Institute Terms and Conditions

6. Figure 5
In vivo lineage tracing reveals Lgr5+ve cells to be cycling stomach stem cells. (A) Restricted expression of Lgr5 in 3–4 cells at the base of the pyloric glands. (B) Left panel: LacZ reporter gene activity initially is activated stochastically in Lgr5+ve cells at the gland base after Tamoxifen administration (black arrows). Right panel: at later time points, entirely Lgr5+ve cell-derived LacZ+ve glandular units are visible throughout the pyloric region. Lgr5 cells continue generating this LacZ+ve epithelium over the entire lifetime of the mouse.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2010 AGA Institute Terms and Conditions

7. Figure 6
In vivo lineage tracing reveals adult Lgr5+ve and Lgr6+ve cells to be cycling skin stem cells. (A) Various stem cell populations responsible for maintaining hair follicle/epidermal self-renewal in adult skin. (B) Left panel: LacZ reporter gene activity initially is activated stochastically in Lgr5+ve cells at the base of the bulge after Tamoxifen administration in Lgr5-EGFP-ires-CreERT2/Rosa-lacZ mice (black arrow). Right panel: at later time-points, Lgr5+ve cell-derived LacZ+ve hair follicles are visible throughout the skin. (C) Left panel: LacZ reporter gene activity initially is activated stochastically in Lgr6+ve cells above the bulge after Tamoxifen administration in Lgr6-EGFP-ires-CreERT2/Rosa-lacZ mice (black arrow). Right panel: at later time points, Lgr6+ve cell-derived LacZ+ve sebaceous glands (black arrow) and epidermis (red arrows) are visible throughout the skin. Both the Lgr5 and Lgr6 populations continue generating the lacZ+ve epithelium over the entire lifetime of the mouse.
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2010 AGA Institute Terms and Conditions