Intestinal Crypt Homeostasis Results from Neutral Competition between Symmetrically Dividing Lgr5 Stem Cells
Intestinal Crypt Homeostasis Results from Neutral Competition between Symmetrically Dividing Lgr5 Stem Cells
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DOI：
10.1016/j.cell.2010.09.016
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发表时间：
2010-10-01
期刊：
影响因子：
64.5
通讯作者：
Clevers, Hans
中科院分区：
文献类型：
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作者：
Snippert, Hugo J.;van der Flier, Laurens G.;Clevers, Hans
肠道干细胞以高表达Lgr5为特征，位于小肠隐窝底部的Paneth细胞之间，每天分裂。我们已经通过产生一个多色Cre-Report对单个干细胞进行了命运图谱的绘制。作为一个群体，Lgr5(Hi)干细胞可以持续一生，而隐窝在1-6个月内就会走向克隆化。我们收集了单个Lgr5(Hi)细胞的短期和长期克隆跟踪数据。这表明大多数Lgr5(Hi)细胞分裂是对称发生的，不支持Lgr5(Hi)细胞分裂产生的两个子细胞采取不同命运的模型(即每个分裂一个Lgr5(Hi)细胞和一个运输放大[TA]细胞)。细胞动力学与一个模型一致，在该模型中，常驻干细胞的数量每天翻一番，并随机采用干细胞或TA命运。定量分析表明，干细胞周转遵循中性漂移动力学模式。
Intestinal stem cells, characterized by high Lgr5 expression, reside between Paneth cells at the small intestinal crypt base and divide every day. We have carried out fate mapping of individual stem cells by generating a multicolor Cre-reporter. As a population, Lgr5(hi) stem cells persist life-long, yet crypts drift toward clonality within a period of 1-6 months. We have collected short- and long-term clonal tracing data of individual Lgr5(hi) cells. These reveal that most Lgr5(hi) cell divisions occur symmetrically and do not support a model in which two daughter cells resulting from an Lgr5(hi) cell division adopt divergent fates (i.e., one Lgr5(hi) cell and one transit-amplifying [TA] cell per division). The cellular dynamics are consistent with a model in which the resident stem cells double their numbers each day and stochastically adopt stem or TA fates. Quantitative analysis shows that stem cell turnover follows a pattern of neutral drift dynamics.