Topography of epithelial–mesenchymal plasticity

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...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2018-06, Vol.115 (23), p.5902-5907
Main Authors: Font-Clos, Francesc, Zapperi, Stefano, La Porta, Caterina A. M.
Format: Article
Language:English
Subjects:
Biological Sciences
Boolean algebra
Cancer
Cell Line, Tumor
Computer simulation
Databases, Genetic
Elastoplasticity
Embryogenesis
Embryonic growth stage
Energy measurement
Epigenesis, Genetic - genetics
Epigenetics
Epithelial-Mesenchymal Transition - genetics
Fractals
Free energy
Gene expression
Genotype & phenotype
Humans
Materials science
Mathematical models
Mesenchyme
Models, Statistical
Neoplasms - genetics
Neoplasms - metabolism
Phenotype
Phenotypic plasticity
Physical Sciences
Plastic properties
Plasticity
Statistical methods
Stem cells
Topographic mapping
Topographic maps
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1722609115