Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
Institute of Molecular Genetics of the ASCR, Prague, Czech Republic.
Nature. 2018 Jun;558(7710):449-453. doi: 10.1038/s41586-018-0190-3. Epub 2018 Jun 6.
Wnt-β-catenin signalling plays a pivotal role in the homeostasis of the intestinal epithelium by promoting stem cell renewal. In the small intestine, epithelial Paneth cells secrete Wnt ligands and thus adopt the function of the stem cell niche to maintain epithelial homeostasis. 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.
Wnt-β-catenin 信号通路通过促进干细胞更新在维持肠道上皮细胞稳态方面发挥着关键作用。在小肠中，上皮细胞潘氏细胞分泌 Wnt 配体，从而发挥干细胞龛的功能来维持上皮细胞稳态。目前尚不清楚结肠中的干细胞龛由哪些细胞组成。本文中，作者发现黏膜下的间质 GLI1 表达细胞形成了这个必需的龛位。阻断 GLI1 表达细胞分泌 Wnt 会阻止小鼠结肠干细胞的更新：干细胞丢失，因此结肠上皮的完整性被破坏，导致死亡。GLI1 表达细胞在小肠的维持中也起着重要作用，它们作为 Wnt 的储备来源，当上皮细胞分泌 Wnt 受到抑制时，这种储备来源变得至关重要。本文数据表明，通过间质 GLI1 表达细胞数量的适应性变化来调节干细胞龛，以满足肠道的需求，这是一种可能的机制。
