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

John D. West, Richard L. Mort, Robert E. Hill, Steven D. Morley, J. Martin Collinson

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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.
Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalStem Cell Research
Volume30
Early online date13 May 2018
DOIs
Publication statusPublished - Jul 2018

Fingerprint

Computer Simulation
Stem Cells
Epithelial Cells
Corneal Epithelium
Clone Cells
Mosaicism
Adrenal Cortex
Reporter Genes
Cornea
Cell Biology
Cell Count
Gene Expression

Keywords

  • Stem cell loss
  • Stem cell replacement
  • Stem cell neutral drift
  • Limbal epithelial stem cell
  • Corneal epithelium
  • Loss of mosaicism

Cite this

Computer simulation of neutral drift among limbal epithelial stem cells of mosaic mice. / West, John D.; Mort, Richard L.; Hill, Robert E.; Morley, Steven D.; Collinson, J. Martin.

In: Stem Cell Research, Vol. 30, 07.2018, p. 1-11.

Research output: Contribution to journalArticle

West, John D. ; Mort, Richard L. ; Hill, Robert E. ; Morley, Steven D. ; Collinson, J. Martin. / Computer simulation of neutral drift among limbal epithelial stem cells of mosaic mice. In: Stem Cell Research. 2018 ; Vol. 30. pp. 1-11.
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note = "Acknowledgements We thank Graham West for writing the software that made this study possible and Ronnie Grant for help with some of the figures. Disclosure of potential conflicts of interest The authors indicate no potential conflicts of interest. Funding information This work was supported by the UK Biotechnology and Biological Sciences Research Council (grants BB/J015172/1 and BB/J015237/1).",
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