Multistability and Multicellularity: Cell Fates as High-Dimensional Attractors of Gene Regulatory Networks

This chapter reviews the biology of cell fate regulation from a “systems” perspective and discusses two gene network models to illustrate how molecular interactions produce multistability and attractors. Traditionally, an individual protein that is expressed only in a certain cell type is referred to as a cell-type specific marker. More detailed analysis based on gene expression profiles using DNA microarray technology now reveals that this is an underestimate. Importantly, maintenance of stable cell state and associated gene expression need not and cannot solely depend on the covalent changes that enjoy the intuitive attribute of stability. If a discrete cell fate is defined by the activation configuration of a set of genes, and all cells harbor the same set of genes, realization of a cell fate will require the general ability of a system of interacting elements to display multiple alternative, discrete stable states. For the Boolean network ensemble approach, such variation of control parameters can be thought of as a response to other components of the system or to external perturbations and hence are captured by the changes in the value of the variables.