Low dimensionality of phenotypic space as an emergent property of coordinated teams in biological regulatory networks

Cell-fate decisions are driven by complex regulatory networks. Despite their complexity, these networks often exhibit low-dimensional dynamics and allow only a limited number of phenotypes. What design principles in network topology allows for these salient features remains unclear. Previously, we demonstrated that networks driving epithelial-mesenchymal transition (EMT) were comprised of two well-coordinated teams of nodes engaged in mutual antagonism; one team drove an epithelial phentoype, while the one reinforced a mesenchymal one, thus canalizing cell-fate decisions. However, it remains elusive whether teams can drive low-dimensional dynamics of such networks. Here, we investigate networks acrosss diverse biological scenarios (EMT, small cell lung cancer, pluripotency, gonadal cell-fate) and show that they all comprise of two teams of nodes which can be identified without simulations, and drive two mutually exclusive phenotypes. Moreover, a stronger team strength associates with low dimensionality in the emergent phenotypic space. Our analysis elucidates how the presence of teams may be a fundamental design principle in networks driving cellular decision-making. ### Competing Interest Statement The authors have declared no competing interest.