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

Mariaceleste Aragona, Alejandro Sifrim, Milan Malfait, Yura Song, Jens Herck, Sophie Dekoninck, Souhir Gargouri, Gaëlle Lapouge, Benjamin Swedlund, Christine Dubois, Pieter Baatsen, Katlijn Vints, Seungmin Han, Fadel Tissir, Thierry Voet, Benjamin D. Simons () and Cédric Blanpain ()
Additional contact information
Mariaceleste Aragona: Université Libre de Bruxelles
Alejandro Sifrim: University of Leuven, KU Leuven
Milan Malfait: Université Libre de Bruxelles
Yura Song: Université Libre de Bruxelles
Jens Herck: University of Leuven, KU Leuven
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
Fadel Tissir: Université Catholique de Louvain, Institute of Neuroscience, Developmental Neurobiology
Thierry Voet: University of Leuven, KU Leuven
Benjamin D. Simons: University of Cambridge
Cédric Blanpain: Université Libre de Bruxelles

Nature, 2020, vol. 584, issue 7820, 268-273

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41586-020-2555-7

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