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

摘要: ABSTRACT Cells in multicellular organisms exhibit discrete mutually exclusive phenotypic states, such as proliferation, apoptosis, or differentiation into various cell types. Each of these “cell fates” is associated with a particular stable genome-wide gene expression profile defined by 25,000 genes. To explain the collapse hyperastronomical number combinatorially possible configurations those characteristic observable fates, latter have been proposed to be high-dimensional attractors activity state space. Here we review biology fate regulation from “systems” perspective and discuss two network models (small systems differential equations Boolean networks) illustrate how molecular interactions produce multistability attractors. Implications for regulation, stem multipotency, stochastic decisions, cancer are discussed. This chapter also illustrates necessity embracing both pathway details well simplifying abstraction computational biology.