Intestinal label-retaining cells are secretory precursors expressing Lgr5
Intestinal label-retaining cells are secretory precursors expressing Lgr5
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DOI：
10.1038/nature11965
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发表时间：
2013-03-07
期刊：
影响因子：
64.8
通讯作者：
Winton, Douglas J.
中科院分区：
文献类型：
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作者：
Buczacki, Simon J. A.;Zecchini, Heather Ireland;Winton, Douglas J.
肠道上皮细胞的快速更新是由位于腺隐窝底部的少量干细胞实现的。这些干细胞被不同地描述为快速增殖或处于静止状态。到目前为止，一种能协调这两种行为的干细胞功能布局一直难以确定。对于静止细胞的其他解释是，它们作为一种平行的或储备的细胞群，定期或在损伤后取代快速增殖的干细胞；它们的确切性质仍然未知。在此我们表明，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细胞谱系的分化分泌细胞。然而，关键的是我们发现，在肠道损伤后，它们能够大量增殖，并能产生包含主要上皮细胞类型的克隆。因此，静止细胞可以被重新激活到干细胞状态。这些发现确立了静止细胞作为一种有效的克隆形成储备细胞，并为研究它们在诸如结直肠癌和肠道炎症等病理过程中的作用提供了动力。
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.