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

Math Biosci. 1999 Jun;159(1):47-78. doi: 10.1016/s0025-5564(99)00010-3.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Culture Techniques
  • Cell Cycle
  • Cell Differentiation / physiology
  • Computer Simulation
  • Models, Biological*
  • Numerical Analysis, Computer-Assisted
  • Oligodendroglia / cytology*
  • Optic Nerve / cytology
  • Rats
  • Stem Cells / cytology*
  • Stochastic Processes
  • Thyroid Hormones / physiology
  • Time Factors

Substances

  • Thyroid Hormones