Competition for Stem Cell Fate Determinants as a Mechanism for Tissue Homeostasis

Abstract: Stem cells maintain tissues by generating differentiated cell types while simultaneously self-renewing their own population. The mechanisms that allow stem cell populations to function collectively to control their density, maintain robust homeostasis and recover from injury remain elusive. Motivated by recent experimental advances, here we develop a generic and robust mechanism of stem cell self-renewal based on competition for diffusible fate determinants, which exert fate control. Using both analytical methods and stochastic simulations, we show that the mechanism is characterized by signature dynamic and statistical properties, from stem cell density fluctuations and transient large-scale oscillation dynamics during recovery, to scaling clonal dynamics, front-like boundary propagation and features of dynamical 'quantization' of self-renewal zones in localized domains. Based on these findings, we suggest that competition for fate determinants provides a generic and robust mechanism by which stem cells can self-organize to achieve density homeostasis in an open (or 'facultative') niche environment.