Analysis of stochastic stem cell models with control.

Understanding the dynamics of stem cell lineages is of central importance both for healthy and cancerous tissues. We study stochastic population dynamics of stem cells and differentiated cells, where cell decisions, such as proliferation vs. differentiation decisions, or division and death decisions, are under regulation from surrounding cells. The goal is to understand how different types of control mechanisms affect the means and variances of cell numbers. We use the assumption of weak dependencies of the regulatory functions (the controls) on the cell populations near the equilibrium to formulate moment equations. We then study three different methods of closure, showing that they all lead to the same results for the highest order terms in the expressions for the moments. We derive simple explicit expressions for the means and the variances of stem cell and differentiated cell numbers. It turns out that the variance is expressed as an algebraic function of partial derivatives of the controls with respect to the population sizes at the equilibrium. We demonstrate that these findings are consistent with the results previously obtained in the context of particular systems, and also present two novel examples with negative and positive control of division and differentiation decisions. This methodology is formulated without any specific assumptions on the functional form of the controls, and thus can be used for any biological system.