A stochastic model of temporally regulated generation of oligodendrocytes in cell culture.
The results of our previous analyses suggest that O-2A progenitor cells become competent for differentiation in vitro after they complete a certain number of critical mitotic cycles. The number of critical cycles varies from clone to clone and should be thought of as a random variable. We propose an approach to the analysis of oligodendrocyte generation in vitro based on a stochastic model allowing for an arbitrary distribution of this random variable with a finite support. When applied to experimental data on clonal growth and differentiation of purified O-2A progenitor cells obtained from optic nerves of 1 and 7 day-old rats, the model provides a good quantitative description not only of the first two moments (mean and variance) of the number of O-2A progenitor cells and oligodendrocytes at different times after the start of experiment, but of the corresponding distributions as well. As our estimates show, there are scarcely any O-2A progenitor cells that divide in vitro more than twice before they acquire the competence for differentiation. Those O-2A cells that have undergone the critical divisions differentiate into an oligodendrocyte in each of the subsequent mitotic cycles with a certain probability. We give estimates of this probability for O-2A cells under different growth conditions. Our analysis suggests that the effect of thyroid hormone is twofold: it reduces the mean duration of the mitotic cycle for progenitor cells, and it increases the probability of their transformation into oligodendrocytes.
Boucher
K
K
Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City 84108, USA. kenneth.boucher@hci.utah.edu
Yakovlev
A Y
AY
Mayer-Proschel
M
M
Noble
M
M
D000818:Animals; D018929:Cell Culture Techniques; D002453:Cell Cycle; D002454:Cell Differentiation / Q000502:physiology; D003198:Computer Simulation; D008954:Models, Biological; D009716:Numerical Analysis, Computer-Assisted; D009836:Oligodendroglia / Q000166:cytology*; D009900:Optic Nerve / Q000166:cytology; D051381:Rats; D013234:Stem Cells / Q000166:cytology*; D013269:Stochastic Processes; D013963:Thyroid Hormones / Q000502:physiology; D013997:Time Factors
D013963:Thyroid Hormones