A stochastic model of temporally regulated generation of oligodendrocytes in cell culture

The results of our previous analyses suggest that O-2A progenitor cells bec ome competent for differentiation in vitro after they complete a certain nu mber 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 var iable with a finite support. When applied to experimental data on clonal gr owth and differentiation of purified O-2A progenitor cells obtained from op tic 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 nu mber of O-2A progenitor cells and oligodendrocytes at different times after the start of experiment, but of the corresponding distributions as well. A s our estimates show, there are scarcely any O-2A progenitor cells that div ide in vitro more than twice before they acquire the competence for differe ntiation. Those O-2A cells that have undergone the critical divisions diffe rentiate into an oligodendrocyte in each of the subsequent mitotic cycles w ith a certain probability. We give estimates of this probability for O-2A c ells under different growth conditions. Our analysis suggests that the effe ct of thyroid hormone is twofold: it reduces the mean duration of the mitot ic cycle for progenitor cells, and it increases the probability of their tr ansformation into oligodendrocytes. (C) 1999 Elsevier Science Inc. All righ ts reserved.