Modeling the evolution of culture-adapted human embryonic stem cells.
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.
Olariu
Victor
V
Department of Automatic Control and Systems Engineering, University of Sheffield, Mappin Street, Sheffield S1 3JD, UK.
Harrison
Neil J
NJ
Coca
Daniel
D
Gokhale
Paul J
PJ
Baker
Duncan
D
Billings
Steve
S
Kadirkamanathan
Visakan
V
Andrews
Peter W
PW
D000220:Adaptation, Biological; D005075:Biological Evolution; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D008957:Models, Genetic; D009010:Monte Carlo Method