Dynamics and robustness of the cardiac progenitor cell induced pluripotent stem cell network during cell phenotypes transition

Abstract

Robustness is a fundamental characteristic of biological systems since all living systems need to adapt to internal or external perturbations, unpredictable environments, stochastic events and unreliable components, and so on. A long-term challenge in systems biology is to reveal the origin of robustness underlying molecular regulator network. In this study, a simple Boolean model is used to investigate the global dynamic properties and robustness of cardiac progenitor cell (CPC) induced pluripotent stem cell network that governs reprogramming and directed differentiation process. It is demonstrated that two major attractors correspond to source and target cell phenotypes, respectively, and two dominating attracting trajectories characterise the biological pathways between two major cell phenotypes. In particular, the experimentally observed transition between different cell phenotypes can be reproduced and explained theoretically. Furthermore, the robustness of major attractors and trajectories is largely maintained with respect to small perturbations to the network. Taken together, the CPC-induced pluripotent stem cell network is extremely robustly designed for their functions.

Method for identification of sensitive nodes in Boolean models of biological networks

“…We have analysed the perturbed networks solely from the perspective of identification of sensitive nodes. The effect of small perturbations on attractor states and trajectories can lead to better insights about the stability of the phenotype [ 28 ]. Further analysis of the effects of such perturbations on the attractors and their basins of attraction would be desirable but very challenging for large networks even of the order of magnitude of the melanogenesis network.…”

Effects of intrinsic and extrinsic noises on transposons kinetics

“…In a real biological system, the function of an ACR possessing system is protected even against large changes in the overall supply of the system's components. [29,30] The stability of the steady states is determined by the community matrix…”