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C Furusawa

Publications and source records attributed to C Furusawa.

5 recordsLinked to original sources

Theory of robustness of irreversible differentiation in a stem cell system: chaos hypothesis.

Based on an 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 the 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 the loss of multipotency is also discussed. Using our model, some predictions that can be tested experimentally are made for a stem cell system.

Animals↗

Origin of complexity in multicellular organisms.

Through extensive studies of dynamical system modeling cellular growth and reproduction, we find evidence that complexity arises in multicellular organisms naturally through evolution. Without any elaborate control mechanism, these systems can exhibit complex pattern formation with spontaneous cell differentiation. Such systems employ a "cooperative" use of resources and maintain a larger growth speed than simple cell systems, which exist in a homogeneous state and behave "selfishly." The relevance of the diversity of chemicals and reaction dynamics to the growth of a multicellular organism is demonstrated. Chaotic biochemical dynamics are found to provide the multipotency of stem cells.

Cell Communication↗

Complex organization in multicellularity as a necessity in evolution.

By introducing a dynamical system model of a multicellular system, it is shown that an organism with a variety of differentiated cell types and a complex pattern emerges through cell-cell interactions even without postulating any elaborate control mechanism. Such an organism is found to maintain a larger growth speed as an ensemble, by achieving a cooperative use of resources, than do simple homogeneous cells, which behave "selfishly." This suggests that the emergence of multicellular organisms with complex organization is a necessity in evolution. According to our theoretical model, there initially appear multipotent stem cells, which undergo stochastic differentiation to other cell types. With development and differentiation, both the chemical diversity and the complexity of intra-cellular dynamics are decreased, as a general consequence of our system. Robustness of the developmental process is also confirmed.

Biological Evolution↗

Emergence of rules in cell society: differentiation, hierarchy, and stability.

A dynamic model for cell differentiation, where cells with internal chemical reaction dynamics interact with each other and replicate was studied. It led to spontaneous differentiation of cells and determination, as discussed in the isologous diversification. The following features of the differentiation were obtained: (1) hierarchical differentiation from a 'stem' cell to other cell types, with the emergence of the interaction-dependent rules for differentiation; (2) global stability of an ensemble of cells consisting of several cell types, that were sustained by the emergent, autonomous control on the rate of differentiation; (3) existence of several cell colonies with different cell-type distributions. The results provide a novel viewpoint on the origin of a complex cell society, while relevance to some biological problems, especially to the hemopoietic system, is also discussed.

Catalysis↗

Emergence of multicellular organisms with dynamic differentiation and spatial pattern.

The origin of multicellular organisms and the mechanism of development in cell societies are studied by choosing a model with intracellular biochemical dynamics allowing for oscillations, cell-cell interaction through diffusive chemicals on a two-dimensional grid, and state-dependent cell adhesion. Cells differentiate due to a dynamical instability, as described by our "isologous diversification" theory. A fixed spatial pattern of differentiated cells emerges, where spatial information is sustained by cell-cell interactions. This pattern is robust against perturbations. With an adequate cell adhesion force, active cells are release that form the seed of a new generation of multicellular organisms, accompanied by death of the original multicellular unit as a halting state. It is shown that the emergence of multicellular organisms with differentiation, regulation, and life cycle is not an accidental event, but a natural consequence in a system of replicating cells with growth.

Animals↗