Wnt–β-catenin signalling plays a pivotal role in the homeostasis of the intestinal epithelium by promoting stem cell renewal1,2. In the small intestine, epithelial Paneth cells secrete Wnt ligands and thus adopt the function of the stem cell niche to maintain epithelial homeostasis3,4. It is unclear which cells comprise the stem cell niche in the colon. Here we show that subepithelial mesenchymal GLI1-expressing cells form this essential niche. Blocking Wnt secretion from GLI1-expressing cells prevents colonic stem cell renewal in mice: the stem cells are lost and, as a consequence, the integrity of the colonic epithelium is corrupted, leading to death. GLI1-expressing cells also play an important role in the maintenance of the small intestine, where they serve as a reserve Wnt source that becomes critical when Wnt secretion from epithelial cells is prevented. Our data suggest a mechanism by which the stem cell niche is adjusted to meet the needs of the intestine via adaptive changes in the number of mesenchymal GLI1-expressing cells.GLI1-positive cells in the colon secrete Wnt ligands and thereby support homeostasis of intestinal stem cells.

中文翻译：

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表达 GLI1 的间充质细胞形成结肠干细胞必不可少的 Wnt 分泌生态位

Wnt-β-catenin 信号传导通过促进干细胞更新在肠上皮稳态中发挥关键作用 1,2。在小肠中，上皮 Paneth 细胞分泌 Wnt 配体，因此采用干细胞生态位的功能来维持上皮稳态3,4。目前尚不清楚哪些细胞构成结肠中的干细胞生态位。在这里，我们展示了上皮下间充质 GLI1 表达细胞形成了这个重要的生态位。阻断 GLI1 表达细胞的 Wnt 分泌会阻止小鼠结肠干细胞的更新：干细胞丢失，结果结肠上皮的完整性被破坏，导致死亡。表达 GLI1 的细胞在小肠的维持中也发挥着重要作用，当 Wnt 从上皮细胞分泌被阻止时，它们作为备用 Wnt 来源变得至关重要。我们的数据表明了一种机制，通过间充质 GLI1 表达细胞数量的适应性变化来调整干细胞生态位以满足肠道需求。结肠中的 GLI1 阳性细胞分泌 Wnt 配体，从而支持肠道干细胞的稳态细胞。