Computer simulation of neutral drift among limbal epithelial stem cells of mosaic mice.
Computer simulation of neutral drift among limbal epithelial stem cells of mosaic mice.
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DOI：
10.1016/j.scr.2018.05.003
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发表时间：
2018-07
影响因子：
1.2
通讯作者：
Collinson JM
中科院分区：
文献类型：
--
作者：
West JD;Mort RL;Hill RE;Morley SD;Collinson JM
使用嵌合体的小鼠作为报告基因表达的基础，是干细胞生物学中许多谱系追踪研究的基础。例如，在马赛克LacZ报告鼠身上，研究表明，角膜周围的角膜缘上皮干细胞(LESCs)维持着角膜上皮的放射状扇区，而且放射状条纹的数量随着年龄的增长而下降。最初，角膜结果被解释为一些LESC克隆的进行性、与年龄相关的丢失或不可逆转的失活。在这项研究中，我们使用计算机模拟表明，这些结果也可以解释为LESC被邻近的LESC随机替换，导致LESC种群的中性漂移。这被证明减少了LESCs的相关克隆的数量，因此将在不减少LESCs的绝对数量的情况下粗化角膜上皮中的马赛克图案。模拟还显示，当LESC被非随机分组时，校正的条纹数目下降得更慢，并且除非模拟的LESC数目低得不切实际，否则镶嵌很少丢失。讨论了马赛克角膜上皮细胞与其他系统(如肾上腺皮质和肠腺)的年龄相关变化不同的可能原因。模拟了马赛克小鼠角膜条纹的年龄相关性减少。干细胞丢失和/或干细胞替换减少了模拟条带的数量。干细胞置换在没有减少干细胞数量的情况下，导致了中性漂移。干细胞聚集成更大的群体会导致条纹数量下降的速度变慢。替换很少会导致嵌合体的丧失，除非干细胞很少。
The use of mice that are mosaic for reporter gene expression underlies many lineage-tracing studies in stem cell biology. For example, using mosaic LacZ reporter mice, it was shown that limbal epithelial stem cells (LESCs) around the periphery of the cornea maintain radial sectors of the corneal epithelium and that radial stripe numbers declined with age. Originally, the corneal results were interpreted as progressive, age-related loss or irreversible inactivation of some LESC clones. In this study we used computer simulations to show that these results could also be explained by stochastic replacement of LESCs by neighbouring LESCs, leading to neutral drift of LESC populations. This was shown to reduce the number of coherent clones of LESCs and hence would coarsen the mosaic pattern in the corneal epithelium without reducing the absolute number of LESCs. Simulations also showed that corrected stripe numbers declined more slowly when LESCs were grouped non-randomly and that mosaicism was rarely lost unless simulated LESC numbers were unrealistically low. Possible reasons why age-related changes differ between mosaic corneal epithelia and other systems, such as adrenal cortices and intestinal crypts, are discussed. Age-related reduction of corneal stripes in mosaic mice was simulated. Stem cell loss and/or stem cell replacement reduced simulated stripe numbers. Stem cell replacement, without reducing stem cell numbers, caused neutral drift. Clumping of stem cells into larger groups caused slower decline in stripe numbers. Replacement rarely caused loss of mosaicism unless there were few stem cells.
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影响因子：
5.9
作者：
Richardson A;Lobo EP;Delic NC;Myerscough MR;Lyons JG;Wakefield D;Di Girolamo N
通讯作者：
Di Girolamo N
影响因子：
16.6
作者：
Lobo EP;Delic NC;Richardson A;Raviraj V;Halliday GM;Di Girolamo N;Myerscough MR;Lyons JG
通讯作者：
Lyons JG
影响因子：
--
作者：
Mort RL;Ramaesh T;Kleinjan DA;Morley SD;West JD
通讯作者：
West JD
影响因子：
4.6
作者：
Kasetti RB;Gaddipati S;Tian S;Xue L;Kao WW;Lu Q;Li Q
通讯作者：
Li Q
影响因子：
1.2
作者：
Dorà NJ;Hill RE;Collinson JM;West JD
通讯作者：
West JD