Quantitative insight into proliferation and differentiation of oligodendrocyte type 2 astrocytes progenitor cells

Huntsman Cancer Institute, Department of Oncological Sciences, University of Utah, 546 Chipeta Way, Suite 1100, Salt Lake City, UT 84108, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 12/1998; 95(24):14164-7. DOI: 10.1073/pnas.95.24.14164
Source: PubMed


As part of our attempts at understanding fundamental principles that underlie the generation of nondividing terminally differentiated progeny from dividing precursor cells, we have developed approaches to a quantitative analysis of proliferation and differentiation of oligodendrocyte type 2 astrocyte (O-2A) progenitor cells at the clonal level. Owing to extensive previous studies of clonal differentiation in this lineage, O-2A progenitor cells represent an excellent system for such an analysis. Previous studies have resulted in two competing hypotheses; one of them suggests that progenitor cell differentiation is symmetric, the other hypothesis introduces an asymmetric process of differentiation. We propose a general model that incorporates both such extreme hypotheses as special cases. Our analysis of experimental data has shown, however, that neither of these extreme cases completely explains the observed kinetics of O-2A progenitor cell proliferation and oligodendrocyte generation in vitro. Instead, our results indicate that O-2A progenitor cells become competent for differentiation after they complete a certain number of critical mitotic cycles that represent a period of symmetric development. This number varies from clone to clone and may be thought of as a random variable; its probability distribution was estimated from experimental data. Those O-2A cells that have undergone the critical divisions then may differentiate into an oligodendrocyte in each of the subsequent mitotic cycles with a certain probability, thereby exhibiting the asymmetric type of differentiation.

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Available from: Kenneth Boucher
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    • "Several methods have been proposed to analyze clonal data (Nedelman et al., 1985; Yakovlev et al., 1998a, 1998b, 2000; Boucher et al., 1999, 2001; von Collani et al., 1999 Zorin et al., 2000; Hyrien et al., 2005a, 2005b; Hyrien, 2007). All these publications resorted to branching processes to model clonal expansion. "
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    • "It gives rise to data frequently referred to as colony sizes or clonal data. For a few examples of such experiments see Nedelman et al. (1985), Yakovlev et al. (1998a, b, 2000), Boucher et al. (1999) (2001), von Collani et al. (1999), Zorin et al. (2000) or Hyrien et al. (2005a, b). "
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