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Topography of epithelial-mesenchymal plasticity.

ABSTRACT: 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.

SUBMITTER: Font-Clos F

PROVIDER: S-EPMC6003369 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Topography of epithelial-mesenchymal plasticity.

Font-Clos Francesc F Zapperi Stefano S La Porta Caterina A M CAM

Proceedings of the National Academy of Sciences of the United States of America 20180521 23

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, a ...[more]

PMID: 29784817

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