Mechanisms of stretch-mediated skin expansion at single-cell resolution
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
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Journal | Nature |
Volume | 584 |
Issue number | 7820 |
Pages (from-to) | 268-273 |
Number of pages | 6 |
ISSN | 0028-0836 |
DOIs | |
Publication status | Published - Aug 2020 |
Externally published | Yes |
- Adaptor Proteins, Signal Transducing/metabolism, Adherens Junctions/metabolism, Animals, Base Sequence, Cell Cycle Proteins/metabolism, Cell Differentiation/drug effects, Cell Self Renewal/drug effects, Chromatin/drug effects, Chromatin Assembly and Disassembly/drug effects, Clone Cells/cytology, Disease Models, Animal, Extracellular Signal-Regulated MAP Kinases/metabolism, Gene Regulatory Networks/drug effects, Hydrogels/administration & dosage, Mechanotransduction, Cellular/drug effects, Mice, Mice, Transgenic, Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors, Mutation, RNA, Messenger/genetics, RNA-Seq, Single-Cell Analysis, Skin/cytology, Stem Cells/cytology, Trans-Activators/antagonists & inhibitors, Transcription Factor AP-1/metabolism, Transcription, Genetic/drug effects
Research areas
ID: 259566288