Intestinal label-retaining cells are secretory precursors expressing Lgr5

摘要

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.%慢速循环的或静态的干细胞是否与肠腺(肠隐rn窝)中快速循环的干细胞共存是个有很大争rn议的问题。DOuglas Winton及其同事利用个rn新方法来在活体中跟踪慢速循环的“标记滞留rn细胞”(LRCs)，发现了一组具有专注的Panethrn细胞的特征、但仍然表达Lgr5等干细胞标志的rnLRCSs. 这些慢速循环的细胞未经细胞分裂而rn分化成Paneth细胞，但受伤时它们也能重新占rn据干细胞的位置，帮助所有“肠系”(intestinal rnlineage)的再生。这项工作表明，静态细胞的rn确起一个“无性系细胞储备库”的作用，它在rn肠癌和肠炎的病理中可能起一定作用。