Glassy fluctuations in gene regulatory networks

The self-organisation of cells into complex tissues relies on a tight regulation of cell behaviour. The interaction of genes in gene regulatory networks is considered to be a main layer of cell fate regulation. The concentration of gene products, mRNA molecules and proteins, has been shown to be subjected to strong fluctuations. Here, by combining a theoretical framework with single-cell sequencing data, we show that cells can reside in a state where gene expression noise exhibits glass-like properties. Specifically, we develop a theory that maps fluctuations in gene regulatory networks to bipartite asymmetric spin glasses. The dynamics on these networks may be characterized by multiple attractors in a rough landscape and the transition between these attractors are of particular interest in the context of cellular decision making. We show that biologically plausible parameters pose cells in the vicinity of a phase transition to a glass-like phase, where fluctuations are strongly correlated in time and between genes. By mapping these findings to single-cell RNA sequencing we find that stem and progenitor cells exhibit signatures of glassy fluctuations in neural tissues. Our work highlights the possibility that long-lived noise could be a carrier of biological information.