Unbalanced response to growth variations reshapes the cell fate decision landscape

Cell-fate determination involves multiple layers of gene regulatory networks, whereas gene expression is globally modulated by cell growth regardless of specific regulations. Here, we utilize fundamental topology of mutual repression that allows a phenotypic bistability, to examine how such global regulation would affect the stability of phenotypic landscape and the accompanying dynamics of cell-fate determination. We show that the landscape experiences a growth-rate induced bifurcation between monostability and bistability. Theoretical and experimental analyses reveal that this bifurcating deformation of landscape arises from the unbalanced response of gene expression to growth variations. The path of growth transition across the bifurcation would reshape cell-fate decisions. These results illustrate that cell growth-rate, as a global characteristic of cellular physiology, plays a crucial role in cell-fate determinations.