TY - JOUR T1 - Fibroblast state switching orchestrates dermal maturation and wound healing JF - bioRxiv DO - 10.1101/236232 SP - 236232 AU - Emanuel Rognoni AU - Angela Oliveira Pisco AU - Toru Hiratsuka AU - Kalle Sipilä AU - Julio Belmonte AU - Atefeh Atefeh Mobasseri AU - Rui Dilão AU - Fiona M. Watt Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/12/18/236232.abstract N2 - Murine dermis contains functionally and spatially distinct fibroblast lineages that cease to proliferate in early postnatal life. Here we propose a mathematical model in which a negative feedback loop between extracellular matrix (ECM) deposition and fibroblast proliferation determines dermal architecture. Our model faithfully recapitulates 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. ER -