Kaneko, Kunihiko, and Tetsuya Yomo. “Isologous diversification: a theory of cell differentiation.” Bulletin of Mathematical Biology 59, no. 1 (1997): 139-196.
URL1 URL2
An isologous diversification theory for cell differentiation is proposed, based on simulations of interacting cells with biochemical networks and the cell division process following consumption of some chemicals. According to the simulations of the interaction-based dynamical systems model, the following scenario of the cell differentiation is proposed. (1) Up to some threshold number, divisions bring about almost identical cells with synchronized biochemical oscillations. (2) As the number is increased, the oscillations lose synchrony, leading to groups of cells with different phases of oscillations. (3) Amplitudes of oscillation and averaged chemical compositions start to differ by groups of cells. The differentiated behavior of states is transmitted to daughter cells. (4) Recursivity is formed so that the daughter cells keep the identical chemical character. This “memory” is made possible through the transfer of initial conditions. (5) Successive differentiation proceeds.
The mechanism of tumor cell formation, origin of stem cells, anomalous differentiation by transplantations, apoptosis and other features of cell differentiation process are also discussed, with some novel predictions.