Fibroblast state switching orchestrates dermal maturation and wound healing

Emanuel Rognoni; Angela Oliveira Pisco; Toru Hiratsuka; Kalle H. Sipilä; Julio M. Belmonte; Seyedeh Atefeh Mobasseri; Christina Philippeos; Rui Dilão; Fiona M. Watt

doi:10.15252/msb.20178174

Fibroblast state switching orchestrates dermal maturation and wound healing

Emanuel Rognoni, Angela Oliveira Pisco, Toru Hiratsuka, Kalle H. Sipilä, Julio M. Belmonte, Seyedeh Atefeh Mobasseri, Christina Philippeos, Rui Dilão, Fiona M. Watt^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

102 Citations (Scopus)

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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.

Original language	English
Article number	e8174
Journal	Molecular Systems Biology
Volume	14
Issue number	8
Early online date	29 Aug 2018
DOIs	https://doi.org/10.15252/msb.20178174
Publication status	Published - Aug 2018

Keywords

dermis development
fibroblast states
mathematical modelling
tissue architecture
wound healing

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Fibroblast state switching orchestrates_Rognoni_Firstonline29Aug2018_GOLD VoRFinal published version, 11.2 MBLicence: CC BY

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title = "Fibroblast state switching orchestrates dermal maturation and wound healing",

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",

author = "Emanuel Rognoni and Pisco, {Angela Oliveira} and Toru Hiratsuka and Sipil{\"a}, {Kalle H.} and Belmonte, {Julio M.} and Mobasseri, {Seyedeh Atefeh} and Christina Philippeos and Rui Dil{\~a}o and Watt, {Fiona M.}",

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doi = "10.15252/msb.20178174",

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AU - Rognoni, Emanuel

AU - Pisco, Angela Oliveira

AU - Hiratsuka, Toru

AU - Sipilä, Kalle H.

AU - Belmonte, Julio M.

AU - Mobasseri, Seyedeh Atefeh

AU - Philippeos, Christina

AU - Dilão, Rui

AU - Watt, Fiona M.

PY - 2018/8

Y1 - 2018/8

N2 - 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.

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.

KW - dermis development

KW - fibroblast states

KW - mathematical modelling

KW - tissue architecture

KW - wound healing

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Fibroblast state switching orchestrates dermal maturation and wound healing

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Keywords

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