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Theory of Robustness of Irreversible Differentiation in a Stem Cell System: Chaos hypothesis
Based on extensive study of a dynamical systems model of the development of a
cell society, a novel theory for stem cell differentiation and its regulation
is proposed as the ``chaos hypothesis''. Two fundamental features of stem cell
systems - stochastic differentiation of stem cells and the robustness of a
system due to regulation of this differentiation - are found to be general
properties of a system of interacting cells exhibiting chaotic intra-cellular
reaction dynamics and cell division, whose presence does not depend on the
detail of the model. It is found that stem cells differentiate into other cell
types stochastically due to a dynamical instability caused by cell-cell
interactions, in a manner described by the Isologous Diversification theory.
This developmental process is shown to be stable not only with respect to
molecular fluctuations but also with respect to removal of cells. With this
developmental process, the irreversible loss of multipotency accompanying the
change from a stem cell to a differentiated cell is shown to be characterized
by a decrease in the chemical diversity in the cell and of the complexity of
the cellular dynamics. The relationship between the division speed and this
loss of multipotency is also discussed. Using our model, some predictions that
can be tested experimentally are made for a stem cell system.Comment: 31 pages, 10 figures, submitted to Jour. Theor. Bio
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