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Mechanisms of stretch-mediated skin expansion at single-cell resolution

Author

Listed:
  • Mariaceleste Aragona

    (Université Libre de Bruxelles)

  • Alejandro Sifrim

    (University of Leuven, KU Leuven
    Wellcome Trust Sanger Institute)

  • Milan Malfait

    (Université Libre de Bruxelles)

  • Yura Song

    (Université Libre de Bruxelles)

  • Jens Herck

    (University of Leuven, KU Leuven
    Wellcome Trust Sanger Institute)

  • Sophie Dekoninck

    (Université Libre de Bruxelles)

  • Souhir Gargouri

    (Université Libre de Bruxelles)

  • Gaëlle Lapouge

    (Université Libre de Bruxelles)

  • Benjamin Swedlund

    (Université Libre de Bruxelles)

  • Christine Dubois

    (Université Libre de Bruxelles)

  • Pieter Baatsen

    (Electron Microscopy Platform of VIB Bio Imaging Core)

  • Katlijn Vints

    (Electron Microscopy Platform of VIB Bio Imaging Core)

  • Seungmin Han

    (University of Cambridge
    University of Cambridge)

  • Fadel Tissir

    (Université Catholique de Louvain, Institute of Neuroscience, Developmental Neurobiology)

  • Thierry Voet

    (University of Leuven, KU Leuven
    Wellcome Trust Sanger Institute)

  • Benjamin D. Simons

    (University of Cambridge
    University of Cambridge
    University of Cambridge)

  • Cédric Blanpain

    (Université Libre de Bruxelles
    WELBIO, Université Libre de Bruxelles)

Abstract

The ability of the skin to grow in response to stretching has been exploited in reconstructive surgery1. Although the response of epidermal cells to stretching has been studied in vitro2,3, it remains unclear how mechanical forces affect their behaviour in vivo. Here we develop a mouse model in which the consequences of stretching on skin epidermis can be studied at single-cell resolution. Using a multidisciplinary approach that combines clonal analysis with quantitative modelling and single-cell RNA sequencing, we show that stretching induces skin expansion by creating a transient bias in the renewal activity of epidermal stem cells, while a second subpopulation of basal progenitors remains committed to differentiation. Transcriptional and chromatin profiling identifies how cell states and gene-regulatory networks are modulated by stretching. Using pharmacological inhibitors and mouse mutants, we define the step-by-step mechanisms that control stretch-mediated tissue expansion at single-cell resolution in vivo.

Suggested Citation

  • Mariaceleste Aragona & Alejandro Sifrim & Milan Malfait & Yura Song & Jens Herck & Sophie Dekoninck & Souhir Gargouri & Gaëlle Lapouge & Benjamin Swedlund & Christine Dubois & Pieter Baatsen & Katlijn, 2020. "Mechanisms of stretch-mediated skin expansion at single-cell resolution," Nature, Nature, vol. 584(7820), pages 268-273, August.
    • Handle: RePEc:nat:nature:v:584:y:2020:i:7820:d:10.1038_s41586-020-2555-7
    DOI: 10.1038/s41586-020-2555-7
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    Cited by:

    1. Elle Koren & Alona Feldman & Marianna Yusupova & Avihay Kadosh & Egor Sedov & Roi Ankawa & Yahav Yosefzon & Waseem Nasser & Stefanie Gerstberger & Liam B. Kimel & Noa Priselac & Samara Brown & Sam Sha, 2022. "Thy1 marks a distinct population of slow-cycling stem cells in the mouse epidermis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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