{'fraction_non_alphanumeric': 0.012106537530266344, 'fraction_numerical': 0.0, 'mean_word_length': 5.858921161825726, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Topography of epithelial–mesenchymal plasticity

Significance Cells can change their phenotype from epithelial to mesenchymal during development and in cancer progression, where this transition is often associated with metastasis and poor disease prognosis. Here we show this process involves the transit through a multitude of metastable hybrid phenotypes in a way that is similar to the driven dynamics of disordered materials. Our method shows that highly aggressive hybrid epithelial/mesenchymal cell phenotypes are located in metastable regions that can easily switch under external and internal perturbations. We propose a general mapping strategy that can be used for other pathways, providing a useful tool to visualize the ever increasing number of gene expression data obtained from single cells and tissues. The transition between epithelial and mesenchymal states has fundamental importance for embryonic development, stem cell reprogramming, and cancer progression. Here, we construct a topographic map underlying epithelial–mesenchymal transitions using a combination of numerical simulations of a Boolean network model and the analysis of bulk and single-cell gene expression data. The map reveals a multitude of metastable hybrid phenotypic states, separating stable epithelial and mesenchymal states, and is reminiscent of the free energy measured in glassy materials and disordered solids. Our work not only elucidates the nature of hybrid mesenchymal/epithelial states but also provides a general strategy to construct a topographic representation of phenotypic plasticity from gene expression data using statistical physics methods.