Stochastic dynamics of two-compartment models with regulatory mechanisms for hematopoiesis

Ren-Yi Wang (Rice University) #

We present an asymptotic analysis of a stochastic two-compartmental cell proliferation system with regulatory mechanisms. We model the system as a state-dependent birth and death process. Proliferation of hematopoietic stem cells (HSCs) is regulated by population density of HSC-derived clones and differentiation of HSC is regulated by population density of HSCs. By scaling up the initial population, we show the density of dynamics converges in distribution to the solution of a system of ordinary differential equations (ODEs). The system of ODEs has a unique non-trivial equilibrium that is globally stable. Furthermore, we show the scaled fluctuation of the population converges in law to a linear diffusion with time-dependent coefficients. With initial data being Gaussian, the limit is a Gauss-Markov process, and it behaves like the FCLT limit under equilibrium with constant coefficients at large times. This is proved by establishing exponential convergence in the 2-Wasserstein metric for the associated Gaussian measures in a \(\mathcal{L}_2\) Hilbert space. We apply our results to analyze and compare two regulatory mechanisms in the hematopoietic system. Simulations are conducted to verify our large-scale and long-time approximation of the dynamics. We demonstrate some regulatory mechanisms are efficient (converge to steady state rapidly) but not effective (have large fluctuation around the steady state).