Mathematical Modeling of Plasticity and Heterogeneity in EMT

Methods Mol Biol. 2021:2179:385-413. doi: 10.1007/978-1-0716-0779-4_28.

Abstract

The epithelial-mesenchymal transition (EMT) and the corresponding reverse process, mesenchymal-epithelial transition (MET), are dynamic and reversible cellular programs orchestrated by many changes at both 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 during an 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 when 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 heterogenous 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.

Keywords: Epithelial-mesenchymal heterogeneity; Epithelial-mesenchymal plasticity; Mathematical modeling; Multi-stability; Nongenetic heterogeneity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Division
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism
  • Epithelial-Mesenchymal Transition*
  • Gene Regulatory Networks
  • Humans
  • Models, Theoretical*
  • Signal Transduction