RT Journal Article
SR Electronic
T1 Fibroblast state switching orchestrates dermal maturation and wound healing
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 236232
DO 10.1101/236232
A1 Emanuel Rognoni
A1 Angela Oliveira Pisco
A1 Toru Hiratsuka
A1 Kalle Sipilä
A1 Julio M. Belmonte
A1 Seyedeh Atefeh Mobasseri
A1 Christina Philippeos
A1 Rui Dilão
A1 Fiona M. Watt
YR 2018
UL http://biorxiv.org/content/early/2018/06/14/236232.abstract
AB 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.Standfirst text We show that fibroblast behaviour switching between two distinct states – proliferating and depositing ECM - is necessary and sufficient to define dermal architecture. Understanding this interdependence is critical for identifying new therapeutic strategies to enhance skin regeneration.HighlightsTissue-scale coordination in murine dermis is driven by the interdependence of cell proliferation and ECM depositionThe tissue architecture is set by a negative feedback loop between ECM deposition/remodelling and proliferationFibroblast lineages lose segregation with ageFibroblast migration is the critical discriminator between dermal development and wound healing