Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
Nature. 2013 Mar 7;495(7439):65-9. doi: 10.1038/nature11965. Epub 2013 Feb 27.
The rapid cell turnover of the intestinal epithelium is achieved from small numbers of stem cells located in the base of glandular crypts. These stem cells have been variously described as rapidly cycling or quiescent. A functional arrangement of stem cells that reconciles both of these behaviours has so far been difficult to obtain. Alternative explanations for quiescent cells have been that they act as a parallel or reserve population that replace rapidly cycling stem cells periodically or after injury; their exact nature remains unknown. Here we show mouse intestinal quiescent cells to be precursors that are committed to mature into differentiated secretory cells of the Paneth and enteroendocrine lineage. However, crucially we find that after intestinal injury they are capable of extensive proliferation and can give rise to clones comprising the main epithelial cell types. Thus, quiescent cells can be recalled to the stem-cell state. These findings establish quiescent cells as an effective clonogenic reserve and provide a motivation for investigating their role in pathologies such as colorectal cancers and intestinal inflammation.
肠道上皮细胞的快速细胞更新是通过位于腺管隐窝底部的少量干细胞来实现的。这些干细胞被描述为快速循环或静止。迄今为止，还很难获得一种能够协调这两种行为的干细胞功能排列。关于静止细胞的另一种解释是，它们作为一个平行或后备群体，周期性或在损伤后替代快速循环的干细胞；它们的确切性质仍然未知。在这里，我们发现小鼠肠道静止细胞是前体细胞，它们注定要成熟为潘氏细胞和肠内分泌谱系的分化分泌细胞。然而，至关重要的是，我们发现，在肠道损伤后，它们能够进行广泛的增殖，并产生包含主要上皮细胞类型的克隆。因此，静止细胞可以被召回干细胞状态。这些发现确立了静止细胞作为一种有效的克隆形成储备，并为研究它们在结直肠癌和肠道炎症等疾病中的作用提供了动力。
