title: Minimal model for stem-cell differentiation.
abstract: To explain the differentiation of stem cells in terms of dynamical systems theory, models of interacting cells with intracellular protein expression dynamics are analyzed and simulated. Simulations were carried out for all possible protein expression networks consisting of two genes under cell-cell interactions mediated by the diffusion of a protein. Networks that show cell differentiation are extracted and two forms of symmetric differentiation based on Turing's mechanism and asymmetric differentiation are identified. In the latter network, the intracellular protein levels show oscillatory dynamics at a single-cell level, while cell-to-cell synchronicity of the oscillation is lost with an increase in the number of cells. Differentiation to a fixed-point-type behavior follows with a further increase in the number of cells. The cell type with oscillatory dynamics corresponds to a stem cell that can both proliferate and differentiate, while the latter fixed-point type only proliferates. This differentiation is analyzed as a saddle-node bifurcation on an invariant circle, while the number ratio of each cell type is shown to be robust against perturbations due to self-consistent determination of the effective bifurcation parameter as a result of the cell-cell interaction. Complex cell differentiation is designed by combing these simple two-gene networks. The generality of the present differentiation mechanism, as well as its biological relevance, is discussed.
authors.affiliation: Research Center for Complex Systems Biology, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Goto
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Kaneko
mesh_terms: D002450:Cell Communication; D002452:Cell Count; D002454:Cell Differentiation; D053263:Gene Regulatory Networks; D042541:Intracellular Space / Q000378:metabolism; D008954:Models, Biological; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism