Isologous Diversification for Robust Development of Cell Society

Isologous diversification, proposed for cell differentiation, is shown to be stable against molecular and other external fluctuations, where amplification of noise-induced slight difference between cells leads to a noise-tolerant society with differentiated cell types. It is a general consequence of interacting cells with biochemical networks and cell divisions, as is confirmed by several model simulations. According to the theory, differentiation proceeds first by loss of synchrony of intracellular oscillations as the number of cells increases. Then the chemical composition of the cells is differentiated. The differentiated compositions become inherited by the next generation, and lead to determined cell types. As a result of successive occurrence of the cell differentiation, the cell society will be composed of different cell types. The whole developmental process is robust not only against molecular fluctuations but also against the removal of a cluster of cells. This robustness is a remarkable feature of isologous diversification, in contrast to the conventional threshold-type mechanism for development. As a testable consequence of the theory, we also discuss interaction-dependent tumor formation and negative correlation between growth speed and chemical diversity.