Topography of epithelial–mesenchymal plasticity

Abstract: The transition between epithelial and mesenchymal states hasfundamental importance for embryonic development, stem cellreprogramming, and cancer progression. Here, we construct atopographic map underlying epithelial–mesenchymal transitionsusing a combination of numerical simulations of a Boolean net-work model and the analysis of bulk and single-cell gene expres-sion data. The map reveals a multitude of metastable hybridphenotypic states, separating stable epithelial and mesenchymalstates, and is reminiscent of the free energy measured in glassymaterials and disordered solids. Our work not only elucidates thenature of hybrid mesenchymal/epithelial states but also providesa general strategy to construct a topographic representation ofphenotypic plasticity from gene expression data using statisticalphysics methods.