Uncontrolled growth resulting from dedifferentiation in a skin cell proliferation model.
By introducing a small backward dedifferentiation probability of postmitotic cells to progenitor cells in a recently proposed skin cell proliferation model, the homeostasis of the system can be disrupted resulting in uncontrolled growth. It is found that when the dedifferentiation probability exceeds a small critical value, the stable fixed point of the system vanishes leading to unlimited cell growth resembling scenarios in carcinogenesis. Explicit expression for the critical dedifferentiation probability and phase diagram are calculated analytically and the associated nonlinear dynamics is analyzed. In the presence of stochastic fluctuations, our model predicts that the escape rate from homeostatic growth to uncontrolled growth is greatly enhanced by a small but finite dedifferentiation probability. These results are verified by numerical solutions of the dynamical system and chemical Langevin equations.
Department of Physics, Graduate Institute of Biophysics and Center for Complex Systems, National Central University, Chungli, Taiwan 320, Republic of China.
J Y
JY
Chang
Pik-Yin
PY
Lai
D002454:Cell Differentiation; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D003198:Computer Simulation; D006801:Humans; D008954:Models, Biological; D015233:Models, Statistical; D012867:Skin / Q000166:cytology* / Q000503:physiopathology*