Quantifying Lgr5-positive stem cell behaviour in the pyloric epithelium.
Quantifying Lgr5-positive stem cell behaviour in the pyloric epithelium.
复制标题
定量幽门上皮中的LGR5阳性干细胞行为。
DOI：
10.1038/srep21923
复制
发表时间：
2016-02-26
影响因子：
4.6
通讯作者：
Pin C
中科院分区：
文献类型：
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作者：
Leushacke M;Barker N;Pin C
使用体内谱系追踪数据，我们量化了幽门胃腺中Lgr 5阳性干细胞群体的克隆扩增以及增殖和分化。拟合克隆扩增模型，我们估计，有五个有效的Lgr 5阳性细胞能够产生单克隆腺体取代对方的中性漂移动力学模式。该分析有助于评估干细胞性能;然而，干细胞增殖不能通过克隆扩增分析定量。我们确定了一个合适的数学模型来量化Lgr 5阳性群体的增殖和分化。正如对稳态群体的预期，Lgr 5阳性群体的增殖率等于其分化率。这一速率明显快于有效细胞被替换的速率，这是通过模拟克隆扩增/收缩来估计的。这表明大多数Lgr 5阳性细胞分裂用于更新上皮细胞，并且只有少数导致有效替换相邻细胞以实现整个腺体的扩张。该模型的应用下改变的情况下，与解耦的分化和增殖进行了演示。这种方法代表了一种有价值的工具，用于量化干细胞在稳态中的表现，重要的是用于破译疾病中改变的干细胞行为。
Using in-vivo lineage tracing data we quantified clonal expansion as well as proliferation and differentiation of the Lgr5-positive stem cell population in pyloric gastric glands. Fitting clone expansion models, we estimated that there are five effective Lgr5-positive cells able to give rise to monoclonal glands by replacing each other following a pattern of neutral drift dynamics. This analysis is instrumental to assess stem cell performance; however, stem cell proliferation is not quantified by clone expansion analysis. We identified a suitable mathematical model to quantify proliferation and differentiation of the Lgr5-positive population. As expected for populations in steady-state, the proliferation rate of the Lgr5-positive population was equal to its rate of differentiation. This rate was significantly faster than the rate at which effective cells are replaced, estimated by modelling clone expansion/contraction. This suggests that the majority of Lgr5-positive cell divisions serve to renew epithelial cells and only few result in the effective replacement of a neighbour to effect expansion to the entire gland. The application of the model under altered situations with uncoupled differentiation and proliferation was demonstrated. This methodology represents a valuable tool for quantifying stem cell performance in homeostasis and importantly for deciphering altered stem cell behaviour in disease.