Olariu Victor, Harrison Neil J, Coca Daniel, Gokhale Paul J, Baker Duncan, Billings Steve, Kadirkamanathan Visakan, Andrews Peter W
Department of Automatic Control and Systems Engineering, University of Sheffield, Mappin Street, Sheffield S1 3JD, UK.
Stem Cell Res. 2010 Jan;4(1):50-6. doi: 10.1016/j.scr.2009.09.001. Epub 2009 Sep 16.
The long-term culture of human embryonic stem (ES) cells is inevitably subject to evolution, since any mutant that arises with a growth advantage will be selectively amplified. However, the evolutionary influences of population size, mutation rate, and selection pressure are frequently overlooked. We have constructed a Monte Carlo simulation model to predict how changes in these factors can influence the appearance and spread of mutant ES cells, and verified its applicability by comparison with in vitro data. This simulation provides an estimate for the expected rate of generation of culture-adapted ES cells under different assumptions for the key parameters. In particular, it highlights the effect of population size, suggesting that the maintenance of cells in small populations reduces the likelihood that abnormal cultures will develop.
人类胚胎干细胞（ES细胞）的长期培养不可避免地会发生进化，因为任何具有生长优势的突变体都会被选择性扩增。然而，群体大小、突变率和选择压力的进化影响常常被忽视。我们构建了一个蒙特卡洛模拟模型，以预测这些因素的变化如何影响突变ES细胞的出现和传播，并通过与体外数据比较验证了其适用性。该模拟为在不同关键参数假设下培养适应性ES细胞的预期产生率提供了估计。特别是，它突出了群体大小的影响，表明在小群体中维持细胞可降低异常培养物出现的可能性。
