Lgr5-expressing chief cells drive epithelial regeneration and cancer in the oxyntic stomach
Lgr5-expressing chief cells drive epithelial regeneration and cancer in the oxyntic stomach
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DOI：
10.1038/ncb3541
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发表时间：
2017-07-01
影响因子：
21.3
通讯作者：
Barker, Nick
中科院分区：
文献类型：
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作者：
Leushacke, Marc;Tan, Si Hui;Barker, Nick
管体上皮细胞的日常更新是由管状腺内的成体干细胞推动的，但这些干细胞的身份仍有争议。lgr 5在多种组织中标记稳态干细胞和“储备”干细胞。在这里，我们报告LGR 5表达在小鼠和人体腺体的主细胞亚群。使用非杂色的Lgr 5 - 2A-CreERT 2小鼠模型，我们通过谱系追踪显示，表达Lgr 5的主细胞在稳态期间不表现为小体干细胞，但被招募作为干细胞，通过激活Wnt信号传导在损伤后影响上皮更新。Lgr 5（+）细胞的消融严重损害了体中上皮的稳态，表明这些Lgr 5（+）细胞在维持稳态干细胞库中的重要作用。我们还将Lgr 5（+）主细胞定义为胃癌的主要起源细胞。这些发现揭示了对体内稳态、修复和癌症的临床相关见解。
The daily renewal of the corpus epithelium is fuelled by adult stem cells residing within tubular glands, but the identity of these stem cells remains controversial. Lgr5 marks homeostatic stem cells and 'reserve' stem cells in multiple tissues. Here, we report Lgr5 expression in a subpopulation of chief cells in mouse and human corpus glands. Using a non-variegated Lgr5-2A-CreERT2 mouse model, we show by lineage tracing that Lgr5-expressing chief cells do not behave as corpus stem cells during homeostasis, but are recruited to function as stem cells to effect epithelial renewal following injury by activating Wnt signalling. Ablation of Lgr5(+) cells severely impairs epithelial homeostasis in the corpus, indicating an essential role for these Lgr5(+) cells in maintaining the homeostatic stem cell pool. We additionally define Lgr5(+) chief cells as a major cell-of-origin of gastric cancer. These findings reveal clinically relevant insights into homeostasis, repair and cancer in the corpus.