STEM CELL PROLIFERATION AND DIFFERENTIATION AND STOCHASTIC BISTABILITY IN GENE EXPRESSION
Zhdanov V.P.

Поступила в редакцию: 23 Августа 2006

PACS: 87.16.-b, 05.40.-a, 05.65.+b

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The process of proliferation and differentiation of stem cells is inherently stochastic in the sense that the outcome of cell division is characterized by probabilities that depend on the intracellular properties, extracellular medium, and cell-cell communication. Despite four decades of intensive studies, the understanding of the physics behind this stochasticity is still limited both in details and conceptually. Here, we suggest a simple scheme showing that the stochastic behavior of a single stem cell may be related to (i) the existence of a short stage of decision whether it will proliferate or differentiate and (ii) control of this stage by stochastic bistability in gene expression or, more specifically, by transcriptional «bursts». Our Monte Carlo simulations indicate that this scheme may operate if the number of mRNA (or protein) generated during the high-reactive periods of gene expression is below or about 50. The stochastic-burst window in the space of kinetic parameters is found to increase with decreasing the mRNA and/or regulatory-protein numbers and increasing the number of regulatory sites. For mRNA production with three regulatory sites, for example, the mRNA degradation rate constant may change in the range %.