Uncertainty in cell fate decision making: Lessons from potential landscapes of bifurcation systems

Abstract

Cell fate decision making is known to be a complex process and is still far from being understood. The intrinsic complexity, but also features such as molecular noise represent challenges for modelling these systems. Waddington’s epigenetic landscape has become the overriding metaphor for developmental processes: it both serves as pictorial representation, and can be related to mathematical models. In this work we investigate how the landscape is affected by noise in the underlying system. Specifically, we focus on those systems where minor changes in the parameters cause major changes in the stability properties of the system, especially bifurcations. We analyse and quantify the changes in the landscape’s shape as the effects of noise increase. We find ample evidence for intricate interplay between noise and dynamics which can lead to qualitative change in a system’s dynamics and hence the corresponding landscape. In particular, we find that the effects can be most pronounced in the vicinity of the bifurcation point of the underlying deterministic dynamical systems, which would correspond to the cell fate decision event in cellular differentiation processes.

Dissecting transition cells from single-cell transcriptome data through multiscale stochastic dynamics

“…The stochastic transitions among attractors considered by MuTrans can be further incorporated with deterministic processes to better understand the cell-fate decision 53 . Despite that the stochastic switching among cell states might be rare in some cases, the local fluctuation of microscopic cell states in gene expression can be prevalent in the microscopic dynamics, therefore the cell-cell scale random walk assumption in MuTrans still holds as a natural assumption.…”