Data- and theory-driven approaches for understanding paths of epithelial-mesenchymal transition

Abstract

Reversible transitions between epithelial and mesenchymal cell states are a crucial form of epithelial plasticity for development and disease progression. Recent experimental data and mechanistic models showed multiple intermediate epithelial-mesenchymal transition (EMT) states as well as trajectories of EMT underpinned by complex gene regulatory networks. In this review, we summarize recent progress in quantifying EMT and characterizing EMT paths with computational methods and quantitative experiments including omics-level measurements. We provide perspectives on how these studies can help relating fundamental cell biology to physiological and pathological outcomes of EMT.

Keywords: fate specification process; genomics process; transcription process.

Figure 1.. Illustration of EMT paths and dynamical systems underpinning EMT/MET.

A. An EMT scoring system allows the identification of intermediate EMT states and paths of EMT. B. Two regulatory networks each capable of producing a tristable EMT system. C-E. Three plausible modes of EMT/MET: signal-driven disappearance of stable steady state (C), noise-driven transitions among stable steady states (D), and limit-cycle-like orbits (E).

Figure 2. Possible mechanistic origin of the conflicting reports on EMT-stemness coupling.

(A) Summary of reports on cell states showing stemness couples with different EMT states along the EMT axis. 1: ref., 2: ref. , 3: ref., 4: ref., 5: ref.. (B) Schematic illustration that the different reports on the EMT-stemness coupling may come from existence of distinct transition paths due to coupling between EMT and other cellular programs, and the weight of each path may be context-dependent.