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Jiang, D. ; Christ, S. ; Correa-Gallegos, D. ; Ramesh, P. ; Kalgudde Gopal, S. ; Wannemacher, J. ; Mayr, C. ; Lupperger, V. ; Yu, Q. ; Ye, H. ; Mück-Häusl, M. ; Rajendran, V. ; Wan, L. ; Liu, J. ; Mirastschijski, U.* ; Volz, T.* ; Marr, C. ; Schiller, H. B. ; Rinkevich, Y.

Injury triggers fascia fibroblast collective cell migration to drive scar formation through N-cadherin.

Nat. Commun. 11:5653 (2020)

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Scars are more severe when the subcutaneous fascia beneath the dermis is injured upon surgical or traumatic wounding. Here, we present a detailed analysis of fascia cell mobilisation by using deep tissue intravital live imaging of acute surgical wounds, fibroblast lineage-specific transgenic mice, and skin-fascia explants (scar-like tissue in a dish – SCAD). We observe that injury triggers a swarming-like collective cell migration of fascia fibroblasts that progressively contracts the skin and form scars. Swarming is exclusive to fascia fibroblasts, and requires the upregulation of N-cadherin. Both swarming and N-cadherin expression are absent from fibroblasts in the upper skin layers and the oral mucosa, tissues that repair wounds with minimal scar. Impeding N-cadherin binding inhibits swarming and skin contraction, and leads to reduced scarring in SCADs and in animals. Fibroblast swarming and N-cadherin thus provide therapeutic avenues to curtail fascia mobilisation and pathological fibrotic responses across a range of medical settings.

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