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Modelling variability and heterogeneity of EMT scenarios highlights nuclear positioning and protrusions as main drivers of extrusion

Author

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  • Steffen Plunder

    (UPS
    University of Vienna
    Sakyo-ku)

  • Cathy Danesin

    (UPS)

  • Bruno Glise

    (UPS)

  • Marina A. Ferreira

    (University of Coimbra)

  • Sara Merino-Aceituno

    (University of Vienna)

  • Eric Theveneau

    (UPS)

Abstract

Epithelial-Mesenchymal Transition (EMT) is a key process in physiological and pathological settings. EMT is often presented as a linear sequence with (i) disassembly of cell-cell junctions, (ii) loss of epithelial polarity and (iii) reorganization of the cytoskeleton leading to basal extrusion from the epithelium. Once out, cells can adopt a migratory phenotype with a front-rear polarity. While this sequence can occur, in vivo observations have challenged it. It is now accepted that multiple EMT scenarios coexist in heterogeneous cell populations. However, the relative importance of each step as well as that of variability and heterogeneity on the efficiency of cell extrusion has not been assessed. Here we used computational modelling to simulate multiple EMT-like scenarios and confronted these data to the EMT of neural crest cells. Overall, our data point to a key role of nuclear positioning and protrusive activity to generate timely basal extrusion.

Suggested Citation

  • Steffen Plunder & Cathy Danesin & Bruno Glise & Marina A. Ferreira & Sara Merino-Aceituno & Eric Theveneau, 2024. "Modelling variability and heterogeneity of EMT scenarios highlights nuclear positioning and protrusions as main drivers of extrusion," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51372-z
    DOI: 10.1038/s41467-024-51372-z
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    1. Toni Celià-Terrassa & Caleb Bastian & Daniel D. Liu & Brian Ell & Nicole M. Aiello & Yong Wei & Jose Zamalloa & Andres M. Blanco & Xiang Hang & Dmitriy Kunisky & Wenyang Li & Elizabeth D. Williams & H, 2018. "Hysteresis control of epithelial-mesenchymal transition dynamics conveys a distinct program with enhanced metastatic ability," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    2. Antti Lignell & Laura Kerosuo & Sebastian J. Streichan & Long Cai & Marianne E. Bronner, 2017. "Identification of a neural crest stem cell niche by Spatial Genomic Analysis," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    3. Ievgenia Pastushenko & Audrey Brisebarre & Alejandro Sifrim & Marco Fioramonti & Tatiana Revenco & Soufiane Boumahdi & Alexandra Van Keymeulen & Daniel Brown & Virginie Moers & Sophie Lemaire & Sarah , 2018. "Identification of the tumour transition states occurring during EMT," Nature, Nature, vol. 556(7702), pages 463-468, April.
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