Identification of stem cells in small intestine and colon by marker gene Lgr5
Identification of stem cells in small intestine and colon by marker gene Lgr5
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DOI：
10.1038/nature06196
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发表时间：
2007-10-25
期刊：
影响因子：
64.8
通讯作者：
Clevers, Hans
中科院分区：
文献类型：
--
作者：
Barker, Nick;van Es, Johan H.;Clevers, Hans
肠上皮是成年哺乳动物中自我更新最快的组织。目前认为，4至6个隐窝干细胞位于小肠中潘氏细胞上方的+4位置;结肠干细胞仍然不确定。Lgr 5（富含亮氨酸重复序列的G蛋白偶联受体5，也称为Gpr 49）因其限制性隐窝表达而选自一组肠Wnt靶基因。在这里，使用两个基因敲入等位基因，我们揭示了独家LGR 5在循环柱状细胞在隐窝基地的表达。此外，Lgr 5在其他几种组织中的稀有细胞中表达。使用诱导型Cre敲入等位基因和Rosa 26-lacZ报告菌株，在成年小鼠中进行谱系追踪实验。Lgr 5阳性的隐窝基底柱状细胞在60天内产生所有上皮细胞系，表明它代表了小肠和结肠的干细胞。Lgr 5的表达模式表明它标志着多种成人组织和癌症中的干细胞。
The intestinal epithelium is the most rapidly self-renewing tissue in adult mammals. It is currently believed that four to six crypt stem cells reside at the +4 position immediately above the Paneth cells in the small intestine; colon stem cells remain undefined. Lgr5 (leucine-rich-repeat-containing G-protein-coupled receptor 5, also known as Gpr49) was selected from a panel of intestinal Wnt target genes for its restricted crypt expression. Here, using two knock-in alleles, we reveal exclusive expression of Lgr5 in cycling columnar cells at the crypt base. In addition, Lgr5 was expressed in rare cells in several other tissues. Using an inducible Cre knock-in allele and the Rosa26-lacZ reporter strain, lineage-tracing experiments were performed in adult mice. The Lgr5-positive crypt base columnar cell generated all epithelial lineages over a 60-day period, suggesting that it represents the stem cell of the small intestine and colon. The expression pattern of Lgr5 suggests that it marks stem cells in multiple adult tissues and cancers.