Journal Article

Lgr4 is required for Paneth cell differentiation and maintenance of intestinal stem cells ex vivo

Van Loy, Tom, Libert, Frédérick, Strollo, Sandra, Mustata, Roxana C, Lefort, Anne, Vassart, Gilbert, Garcia, Marie‐Isabelle

2011

Overview

Gene inactivation of the orphan G protein‐coupled receptor LGR4, a paralogue of the epithelial‐stem‐cell marker LGR5, results in a 50% decrease in epithelial cell proliferation and an 80% reduction in terminal differentiation of Paneth cells in postnatal mouse intestinal crypts. When cultured ex vivo , LGR4‐deficient crypts or progenitors, but not LGR5‐deficient progenitors , die rapidly with marked downregulation of stem‐cell markers and Wnt target genes, including Lgr5 . Partial rescue of this phenotype is achieved by addition of LiCl to the culture medium, but not Wnt agonists. Our results identify LGR4 as a permissive factor in the Wnt pathway in the intestine and, as such, as a potential target for intestinal cancer therapy. Lgr4 , a paralogue of Lgr5 , is also expressed in intestinal crypts. Crypts from Lgr4 hypomorphic mice display signs of defective Wnt signalling: reduced cell proliferation and defective terminal differentiation of Paneth cells in vivo . When cultured ex vivo , the crypts show downregulation of stem cell markers, including Lgr5 , and die rapidly.

• Publisher: John Wiley & Sons, Ltd,Nature Publishing Group UK,Springer Nature B.V,Nature Publishing Group
• Subject: Animals / Cancer / Cell culture / Cell Differentiation / Cell proliferation / Differentiation / EMBO11 / EMBO37 / Epithelial cells / G protein-coupled receptors / Gene Expression Profiling / Gene Expression Regulation, Developmental - drug effects / Gene Knockout Techniques / Genetic markers / GPCR / Inactivation / intestinal crypts / Intestine / Intestines - cytology / Intestines - metabolism / LGR / Lithium chloride / Lithium Chloride - pharmacology / Mice / Mice, Knockout / Molecular biology / Organoids - growth & development / Organoids - metabolism / Paneth cells / Paneth Cells - cytology / Phenotype / Proteins / Receptors, G-Protein-Coupled - genetics / Receptors, G-Protein-Coupled - metabolism / Scientific Report / Scientific Reports / Stem cells / Stem Cells - cytology / Stem Cells - metabolism / Wnt protein