TY - JOUR
T1 - Mechanisms of stretch-mediated skin expansion at single-cell resolution
AU - Aragona, Mariaceleste
AU - Sifrim, Alejandro
AU - Malfait, Milan
AU - Song, Yura
AU - Van Herck, Jens
AU - Dekoninck, Sophie
AU - Gargouri, Souhir
AU - Lapouge, Gaëlle
AU - Swedlund, Benjamin
AU - Dubois, Christine
AU - Baatsen, Pieter
AU - Vints, Katlijn
AU - Han, Seungmin
AU - Tissir, Fadel
AU - Voet, Thierry
AU - Simons, Benjamin D
AU - Blanpain, Cédric
PY - 2020/8
Y1 - 2020/8
N2 - 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.
AB - 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.
KW - Adaptor Proteins, Signal Transducing/metabolism
KW - Adherens Junctions/metabolism
KW - Animals
KW - Base Sequence
KW - Cell Cycle Proteins/metabolism
KW - Cell Differentiation/drug effects
KW - Cell Self Renewal/drug effects
KW - Chromatin/drug effects
KW - Chromatin Assembly and Disassembly/drug effects
KW - Clone Cells/cytology
KW - Disease Models, Animal
KW - Extracellular Signal-Regulated MAP Kinases/metabolism
KW - Gene Regulatory Networks/drug effects
KW - Hydrogels/administration & dosage
KW - Mechanotransduction, Cellular/drug effects
KW - Mice
KW - Mice, Transgenic
KW - Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors
KW - Mutation
KW - RNA, Messenger/genetics
KW - RNA-Seq
KW - Single-Cell Analysis
KW - Skin/cytology
KW - Stem Cells/cytology
KW - Trans-Activators/antagonists & inhibitors
KW - Transcription Factor AP-1/metabolism
KW - Transcription, Genetic/drug effects
U2 - 10.1038/s41586-020-2555-7
DO - 10.1038/s41586-020-2555-7
M3 - Journal article
C2 - 32728211
VL - 584
SP - 268
EP - 273
JO - Nature
JF - Nature
SN - 0028-0836
IS - 7820
ER -