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bioRxiv · 10.1101/2020.01.27.920371

Analyses of Multi-dimensional Single Cell Trajectories Quantify Transition Paths Between Nonequilibrium Steady States

Wang, W.·Xing, J.
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Abstract

How a cell changes from one stable phenotype to another one is a fundamental problem in developmental and cell biology. Epithelial-to-mesenchymal transition (EMT) is a phenotypic transition process extensively studied recently but mechanistic details remain elusive. Through time-lapse imaging we recorded single cell trajectories of human A549/Vim-RFP cells undergoing EMT induced by different concentrations of TGF-{beta} in a multi-dimensional cell feature space. The trajectories cluster into two distinct groups, indicating that the transition dynamics proceeds through parallel paths. We then reconstructed the reaction coordinates and corresponding pseudo-potentials from the trajectories. The potentials reveal a plausible mechanism for the emergence of the two paths as the original stable epithelial attractor collides with two saddle points sequentially with increased TGF-{beta} concentration, and relaxes to a new one. Functionally the directional saddle-node bifurcation ensures a CPT proceeds towards a specific cell type, as a mechanistic realization of the canalization idea proposed by Waddington.

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Wang, W., Xing, J.. 2020-01-28. Analyses of Multi-dimensional Single Cell Trajectories Quantify Transition Paths Between Nonequilibrium Steady States. https://doi.org/10.1101/2020.01.27.920371

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