Computer simulation of neutral drift among limbal epithelial stem cells of mosaic mice

West, John D and Mort, Richard L and Hill, Robert E and Morley, Steven D and Collinson, J Martin (2018) Computer simulation of neutral drift among limbal epithelial stem cells of mosaic mice. Stem Cell Research, 30. pp. 1-11. ISSN 1873-5061

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Abstract

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.

Item Type:
Journal Article
Journal or Publication Title:
Stem Cell Research
Additional Information:
Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/2700
Subjects:
ID Code:
125464
Deposited By:
Deposited On:
24 May 2018 13:12
Refereed?:
Yes
Published?:
Published
Last Modified:
27 Oct 2020 08:04