Structural requirements and discrimination of cell differentiation networks

TL;DR

This study analyzes small gene regulatory networks to identify structural features necessary for multistability in cell differentiation, using qualitative modeling to assess robustness and discriminate network configurations.

Contribution

It introduces a qualitative modeling framework to determine structural network properties essential for multistability in cell differentiation networks.

Findings

Identifies structural network properties necessary for multistability.

Shows the relationship between network structure and robustness.

Provides criteria to discriminate network configurations based on behavior.

Abstract

Mathematical models of stem cell differentiation are commonly based upon the concept of subsequent cell fate decisions, each controlled by a gene regulatory network. These networks exhibit a multistable behavior and cause the system to switch between qualitatively distinct stable steady states. However, the network structure of such a switching module is often uncertain, and there is lack of knowledge about the exact reaction kinetics. In this paper, we therefore perform an elementary study of small networks consisting of three interacting transcriptional regulators responsible for cell differentiation: We investigate which network structures can reproduce a certain multistable behavior, and how robustly this behavior is realized by each network. In order to approach these questions, we use a modeling framework which only uses qualitative information about the network, yet allows model discrimination as well as to evaluate the robustness of the desired multistability properties. We reveal structural network properties which are necessary and sufficient to realize distinct steady state patterns required for cell differentiation. Our results also show that structural and robustness properties of the networks are related to each other.