Lgr4 is required for Paneth cell differentiation and maintenance of intestinal stem cells ex vivo
Lgr4 is required for Paneth cell differentiation and maintenance of intestinal stem cells ex vivo
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DOI：
10.1038/embor.2011.52
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发表时间：
2011-06-01
期刊：
影响因子：
7.7
通讯作者：
Garcia, Marie-Isabelle
中科院分区：
文献类型：
--
作者：
Mustata, Roxana C.;Van Loy, Tom;Garcia, Marie-Isabelle
孤儿G蛋白偶联受体LGR4（上皮干细胞标记物LGR5的同源物）基因失活可导致出生后小鼠肠隐窝上皮细胞增殖减少50%，Paneth细胞终末分化减少80%。在体外培养时，缺乏lgr4的隐窝或祖细胞，而不是缺乏Lgr5的祖细胞，会随着干细胞标记物和Wnt靶基因（包括Lgr5）的显著下调而迅速死亡。这种表型的部分恢复是通过在培养基中添加LiCl而不是Wnt激动剂来实现的。我们的研究结果确定LGR4是肠道Wnt通路中的一个允许因子，因此，它是肠癌治疗的潜在靶点。
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.