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Mol Syst Biol. 2018 Aug 29;14(8):e8174. doi: 10.15252/msb.20178174.

Fibroblast state switching orchestrates dermal maturation and wound healing.

Author information

1
Centre for Stem Cells and Regenerative Medicine, King's College London, London, UK.
2
Developmental Biology Unit and Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
3
Nonlinear Dynamics Group, Instituto Superior Técnico, Lisbon, Portugal.
4
Centre for Stem Cells and Regenerative Medicine, King's College London, London, UK fiona.watt@kcl.ac.uk.

Abstract

Murine dermis contains functionally and spatially distinct fibroblast lineages that cease to proliferate in early postnatal life. Here, we propose a model in which a negative feedback loop between extracellular matrix (ECM) deposition and fibroblast proliferation determines dermal architecture. Virtual-tissue simulations of our model faithfully recapitulate dermal maturation, predicting a loss of spatial segregation of fibroblast lineages and dictating that fibroblast migration is only required for wound healing. To test this, we performed in vivo live imaging of dermal fibroblasts, which revealed that homeostatic tissue architecture is achieved without active cell migration. In contrast, both fibroblast proliferation and migration are key determinants of tissue repair following wounding. The results show that tissue-scale coordination is driven by the interdependence of cell proliferation and ECM deposition, paving the way for identifying new therapeutic strategies to enhance skin regeneration.

KEYWORDS:

dermis development; fibroblast states; mathematical modelling; tissue architecture; wound healing

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