Mathematical Modeling of Plasticity and Heterogeneity in EMT.

@article{Tripathi2021MathematicalMO,
  title={Mathematical Modeling of Plasticity and Heterogeneity in EMT.},
  author={Shubham Tripathi and Jianhua Xing and Herbert Levine and Mohit Kumar Jolly},
  journal={Methods in molecular biology},
  year={2021},
  volume={2179},
  pages={
          385-413
        }
}
The epithelial-mesenchymal transition (EMT) and the corresponding reverse process, mesenchymal-epithelial transition (MET), are dynamic and reversible cellular programs orchestrated by many changes at both biochemical and morphological levels. A recent surge in identifying the molecular mechanisms underlying EMT/MET has led to the development of various mathematical models that have contributed to our improved understanding of dynamics at single-cell and population levels: (a) multi-stability… 

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References

SHOWING 1-10 OF 91 REFERENCES

Hysteresis control of epithelial-mesenchymal transition dynamics conveys a distinct program with enhanced metastatic ability

TLDR
A non-linear hysteretic response of E-cadherin repression during TGFβ-induced EMT that is controlled by the strength of the miR-200s/ZEBs negative feedback loop and enhances metastasis is characterized.

TGF-β–induced epithelial-to-mesenchymal transition proceeds through stepwise activation of multiple feedback loops

TLDR
Experimental and computational analyses identify multiple cell populations during the epithelial-to-mesenchymal transition and provide experimental confirmation for a model of cascading switches in phenotypes associated with TGF-β1–induced EMT of MCF10A cells that involves two double-negative feedback loops.

Stability of the hybrid epithelial/mesenchymal phenotype

TLDR
The results suggest that partial EMT, i.e. a hybrid E/M phenotype, need not be ‘metastable’, and strengthen the emerging notion that partialEMT, but not necessarily a complete E MT, is associated with aggressive tumor progression.

Topography of epithelial–mesenchymal plasticity

TLDR
A topographic map underlying epithelial–mesenchymal transitions is constructed using a combination of numerical simulations of a Boolean network model and the analysis of bulk and single-cell gene expression data, revealing a multitude of metastable hybrid phenotypic states.

EMT and MET: necessary or permissive for metastasis?

TLDR
This work focuses on epithelial-mesenchymal plasticity in metastatic dissemination and proposes alternative mechanisms for successful dissemination and metastases beyond the traditional EMT-MET view.

Towards elucidating the connection between epithelial–mesenchymal transitions and stemness

TLDR
Using a specially devised theoretical framework to investigate the dynamics of the LIN28/let-7 system, it is shown that it can operate as a three-way switch similar to the three- way operation of the miR-200/ZEB circuit that allows for the existence of a hybrid epithelial/mesenchymal (E/M) phenotype.

Notch-Jagged signalling can give rise to clusters of cells exhibiting a hybrid epithelial/mesenchymal phenotype

TLDR
A mechanism-based theoretical model is devised that links cell–cell communication via Notch-Delta-Jagged signalling with the regulation of EMT and offers possible mechanistic insights into the role of Jagged in tumour progression, and offers a framework to investigate the effects of other microenvironmental signals during metastasis.

An Ovol2-Zeb1 Mutual Inhibitory Circuit Governs Bidirectional and Multi-step Transition between Epithelial and Mesenchymal States

TLDR
This work has identified epithelial cells that naturally exist in an intermediate state with bidirectional differentiation potential, and found the balance between EMT-promoting and -inhibiting factors to be critical in achieving and selecting between intermediate states.
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