Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
Cell Stem Cell. 2013 Nov 7;13(5):626-33. doi: 10.1016/j.stem.2013.08.001. Epub 2013 Sep 12.
Lineage-tracing approaches, widely used to characterize stem cell populations, rely on the specificity and stability of individual markers for accurate results. We present a method in which genetic labeling in the intestinal epithelium is acquired as a mutation-induced clonal mark during DNA replication. By determining the rate of mutation in vivo and combining this data with the known neutral-drift dynamics that describe intestinal stem cell replacement, we quantify the number of functional stem cells in crypts and adenomas. Contrary to previous reports, we find that significantly lower numbers of "working" stem cells are present in the intestinal epithelium (five to seven per crypt) and in adenomas (nine per gland), and that those stem cells are also replaced at a significantly lower rate. These findings suggest that the bulk of tumor stem cell divisions serve only to replace stem cell loss, with rare clonal victors driving gland repopulation and tumor growth.
谱系追踪方法广泛用于描述干细胞群体，其结果的准确性依赖于单个标记的特异性和稳定性。我们提出了一种方法，其中肠道上皮中的遗传标记是在 DNA 复制过程中作为突变诱导的克隆标记获得的。通过确定体内的突变率，并将这些数据与描述肠道干细胞替代的已知中性漂移动力学相结合，我们定量了隐窝和腺瘤中功能性干细胞的数量。与之前的报告相反，我们发现肠道上皮（每个隐窝五到七个）和腺瘤（每个腺体九个）中存在的“工作”干细胞数量明显减少，并且这些干细胞的替换速度也明显降低。这些发现表明，肿瘤干细胞分裂的大部分仅用于替代干细胞的损失，而罕见的克隆胜利者驱动腺体的再增殖和肿瘤的生长。
