Barker Nick, van Es Johan H, Kuipers Jeroen, Kujala Pekka, van den Born Maaike, Cozijnsen Miranda, Haegebarth Andrea, Korving Jeroen, Begthel Harry, Peters Peter J, Clevers Hans
Hubrecht Institute, Uppsalalaan 8, 3584CT Utrecht, The Netherlands.
Nature. 2007 Oct 25;449(7165):1003-7. doi: 10.1038/nature06196. Epub 2007 Oct 14.
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.
肠上皮是成年哺乳动物中自我更新最快的组织。目前认为，在小肠中，4至6个隐窝干细胞位于潘氏细胞上方紧邻的+4位置；结肠干细胞仍未明确。富含亮氨酸重复序列的G蛋白偶联受体5（Lgr5，也称为Gpr49）因其在隐窝中的限制性表达，从一组肠道Wnt靶基因中被筛选出来。在此，我们利用两个敲入等位基因，揭示了Lgr5在隐窝底部循环柱状细胞中的特异性表达。此外，Lgr5在其他几种组织的罕见细胞中也有表达。利用可诱导的Cre敲入等位基因和Rosa26 - lacZ报告菌株，在成年小鼠中进行了谱系追踪实验。Lgr5阳性的隐窝底部柱状细胞在60天内产生了所有上皮谱系，这表明它代表小肠和结肠的干细胞。Lgr5的表达模式表明它可标记多种成年组织和癌症中的干细胞。
