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.
Topography of epithelial-mesenchymal plasticity / F. Font-Clos, S. Zapperi, C. La Porta. - In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - ISSN 0027-8424. - (2018 May 21). [Epub ahead of print] [10.1073/pnas.1722609115]
Topography of epithelial-mesenchymal plasticity
F. Font-ClosPrimo
;S. ZapperiSecondo
;C. La PortaUltimo
2018
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.File | Dimensione | Formato | |
---|---|---|---|
LandscapeEMT_PNAS_rev1.pdf
Open Access dal 26/11/2018
Tipologia:
Post-print, accepted manuscript ecc. (versione accettata dall'editore)
Dimensione
9.48 MB
Formato
Adobe PDF
|
9.48 MB | Adobe PDF | Visualizza/Apri |
5902.full.pdf
accesso aperto
Tipologia:
Publisher's version/PDF
Dimensione
1.85 MB
Formato
Adobe PDF
|
1.85 MB | Adobe PDF | Visualizza/Apri |
Pubblicazioni consigliate
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.