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

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Aragona, Mariaceleste 
Sifrim, Alejandro 

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.

Description

Keywords

Adaptor Proteins, Signal Transducing, Adherens Junctions, Animals, Base Sequence, Cell Cycle Proteins, Cell Differentiation, Cell Self Renewal, Chromatin, Chromatin Assembly and Disassembly, Clone Cells, Disease Models, Animal, Extracellular Signal-Regulated MAP Kinases, Gene Regulatory Networks, Hydrogels, Mechanotransduction, Cellular, Mice, Mice, Transgenic, Mitogen-Activated Protein Kinase Kinases, Mutation, RNA, Messenger, RNA-Seq, Single-Cell Analysis, Skin, Stem Cells, Trans-Activators, Transcription Factor AP-1, Transcription, Genetic, YAP-Signaling Proteins

Journal Title

Nature

Conference Name

Journal ISSN

0028-0836
1476-4687

Volume Title

584

Publisher

Springer Science and Business Media LLC

Rights

All rights reserved
Sponsorship
Wellcome Trust (098357/Z/12/Z)
Royal Society (RP/R1/180165)
Wellcome Trust (092096/Z/10/Z)
Cancer Research Uk (None)
Medical Research Council (MC_PC_12009)
Medical Research Council (MC_PC_17230)
Wellcome Trust Royal Society