Lineage Tracing Reveals Lgr5+ Stem Cell Activity in Mouse Intestinal Adenomas
Lineage Tracing Reveals Lgr5+ Stem Cell Activity in Mouse Intestinal Adenomas
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DOI：
10.1126/science.1224676
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发表时间：
2012-08-10
期刊：
影响因子：
56.9
通讯作者：
Clevers, Hans
中科院分区：
文献类型：
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作者：
Schepers, Arnout G.;Snippert, Hugo J.;Clevers, Hans
肿瘤由专门的干细胞维持的概念，即所谓的癌症干细胞假说，引起了人们极大的兴趣，但仍存在争议。通过研究小鼠模型，我们为原发性肠腺瘤（肠癌的前兆）中存在干细胞活性提供了直接的功能性证据。通过使用R26 R-Confetti报告基因的“谱系追溯”，我们证明了隐窝干细胞标志物Lgr 5（富含亮氨酸的重复序列的异源三聚体鸟嘌呤核苷酸结合蛋白偶联受体5）也标志着一个腺瘤细胞亚群，该细胞亚群促进了已建立的肠腺瘤的生长。这些Lgr 5（+）细胞，占腺瘤细胞的约5%至10%，产生额外的Lgr 5（+）细胞以及所有其他腺瘤细胞类型。Lgr 5（+）细胞与潘氏细胞在腺瘤基底附近混杂，这一模式使人联想到正常隐窝龛的结构。
The concept that tumors are maintained by dedicated stem cells, the so-called cancer stem cell hypothesis, has attracted great interest but remains controversial. Studying mouse models, we provide direct, functional evidence for the presence of stem cell activity within primary intestinal adenomas, a precursor to intestinal cancer. By "lineage retracing" using the multicolor Cre-reporter R26R-Confetti, we demonstrate that the crypt stem cell marker Lgr5 (leucine-rich repeat-containing heterotrimeric guanine nucleotide-binding protein-coupled receptor 5) also marks a subpopulation of adenoma cells that fuel the growth of established intestinal adenomas. These Lgr5(+) cells, which represent about 5 to 10% of the cells in the adenomas, generate additional Lgr5(+) cells as well as all other adenoma cell types. The Lgr5(+) cells are intermingled with Paneth cells near the adenoma base, a pattern reminiscent of the architecture of the normal crypt niche.