Mathematical Modeling of Plasticity and Heterogeneity in EMT

TL;DR

This paper reviews mathematical models of EMT/MET, highlighting their role in understanding cellular heterogeneity, reversibility, and dynamics during phenotypic transitions in epithelial-mesenchymal processes.

Contribution

It introduces various mathematical modeling approaches that elucidate EMT/MET dynamics and heterogeneity at single-cell and population levels.

Findings

Models reveal multi-stability in cell phenotypes.

Identification of tipping points for irreversibility.

Insights into non-cell autonomous effects on EMT.

Abstract

Epithelial-Mesenchymal Transition (EMT), and the corresponding reverse process, Mesenchymal-Epithelial Transition (MET), are dynamic and reversible cellular programs orchestrated by many changes at biochemical and morphological levels. A recent surge in identifying the molecular mechanisms underlying EMT/MET has led to the development of various mathematical models that have contributed to our improved understanding of dynamics at single-cell and population levels: a) multi-stability (how many phenotypes can cells attain en route EMT/MET?), b) reversibility/irreversibility (what time and/or concentration of an EMT inducer marks the 'tipping point' when cells induced to undergo EMT cannot revert?), c) symmetry in EMT/MET (do cells take the same path while reverting as they took during the induction of EMT?), and d) non-cell autonomous mechanisms (how does a cell undergoing EMT alter the tendency of its neighbors to undergo EMT?). These dynamical traits may facilitate a heterogeneous response within a cell population undergoing EMT/MET. Here, we present a few examples of designing different mathematical models that can contribute to decoding EMT/MET dynamics.