Abstract

Elucidating the principles of cellular decision-making is of fundamental importance. These decisions are often orchestrated by underlying regulatory networks. While we understand the dynamics of simple network motifs, how large networks lead to a limited number of phenotypes, despite their complexity, remains largely elusive. Here, we investigated multiple different networks governing cellular plasticity engaged in cancer metastasis and identified a latent design principle in their topology that limits their phenotypic repertoire – the presence of two “teams” of nodes engaging in a mutually inhibitory feedback loop, forming a toggle switch. These “teams” are specific to these networks and directly shape the phenotypic landscape and consequently the frequency and stability of terminal phenotypes vs. the intermediary ones. Our analysis reveals that network topology alone can contain information about phenotypic distributions it can lead to, thus obviating the need to simulate them. We present experimental evidence of such “teams” in transcriptomic datasets across many contexts and unravel topological signatures that can drive canalization of cell-fates during decision-making processes.

The seminar will be held in the JDB Seminar Room, Department of Engineering, and online (zoom): https://us06web.zoom.us/j/87986687566?pwd=MGJScmMwd2lwT0tVMHNmWmxSa05XZz09