Modeling the evolution of culture-adapted human embryonic stem cells

Research output: Contribution to journalArticle

Abstract

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.

Details

Authors
  • Victor Olariu
  • Neil J. Harrison
  • Daniel Coca
  • Paul J. Gokhale
  • Duncan Baker
  • Steve Billings
  • Visakan Kadirkamanathan
  • Peter W. Andrews
External organisations
  • University of Sheffield
  • Sheffield Children's Trust
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology
  • Biophysics
Original languageEnglish
Pages (from-to)50-56
Number of pages7
JournalStem Cell Research
Volume4
Issue number1
Publication statusPublished - 2010 Jan
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes