Intermittent ERK oscillations downstream of FGF in mouse embryonic stem cells

Abstract

Signal transduction networks process extracellular signals to guide cell fate decisions such as to divide, differentiate, or die. These networks can generate characteristic dynamic activities that are shaped by their cell-type specific architecture. The differentiation of pluripotent cells is controlled by FGF/ERK signaling. However, the dynamic activity of the FGF/ERK signaling network in this context remains unexplored. Here we use live cell sensors in wild type and Fgf4 mutant mouse embryonic stem cells to measure ERK dynamic activity in single cells, in response to defined ligand concentrations. We find that ERK activity oscillates in embryonic stem cells. Single cells can transit between oscillatory and non-oscillatory behavior, leading to heterogeneous dynamic activities in the population. Oscillations become more prevalent with increasing FGF4 dose, while maintaining a robust characteristic timescale. Our results suggest that FGF/ERK signaling operates in the vicinity of a transition point between oscillatory and non-oscillatory dynamics in embryonic stem cells.