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Sinha, Sarthak; Sparks, Holly D.; Labit, Elodie; Robbins, Hayley N.; Gowing, Kevin; Jaffer, Arzina; Kutluberk, Eren; Arora, Rohit; Raredon, Micha Sam Brickman; Cao, Leslie; Swanson, Scott; Jiang, Peng; Hee, Olivia; Pope, Hannah; Workentine, Matt; Todkar, Kiran; Sharma, Nilesh; Bharadia, Shyla; Chockalingam, Keerthana; de Almeida, Luiz G.N.; Adam, Mike; Niklason, Laura; Potter, S. Steven; Seifert, Ashley W.; Dufour, Antoine; Gabriel, Vincent; Rosin, Nicole L.; Stewart, Ron; Muench, Greg; McCorkell, Robert; Matyas, John; Biernaskie, Jeff
Cell, 12/2022, Letnik: 185, Številka: 25Journal Article
Adult mammalian skin wounds heal by forming fibrotic scars. We report that full-thickness injuries of reindeer antler skin (velvet) regenerate, whereas back skin forms fibrotic scar. Single-cell multi-omics reveal that uninjured velvet fibroblasts resemble human fetal fibroblasts, whereas back skin fibroblasts express inflammatory mediators mimicking pro-fibrotic adult human and rodent fibroblasts. Consequently, injury elicits site-specific immune responses: back skin fibroblasts amplify myeloid infiltration and maturation during repair, whereas velvet fibroblasts adopt an immunosuppressive phenotype that restricts leukocyte recruitment and hastens immune resolution. Ectopic transplantation of velvet to scar-forming back skin is initially regenerative, but progressively transitions to a fibrotic phenotype akin to the scarless fetal-to-scar-forming transition reported in humans. Skin regeneration is diminished by intensifying, or enhanced by neutralizing, these pathologic fibroblast-immune interactions. Reindeer represent a powerful comparative model for interrogating divergent wound healing outcomes, and our results nominate decoupling of fibroblast-immune interactions as a promising approach to mitigate scar. Display omitted •Reindeer antler velvet regenerates after wounding whereas back skin forms a scar•Fibroblasts direct site-specific immune cell recruitment and differentiation•Fibroblast fate reversion and absence of inflammatory signals enables regeneration•Obstructing fibroblast inflammatory signals enhances skin regeneration The particular properties of reindeer antler velvet are leveraged here to identify which factors lead to scarring versus regenerative healing in mammalian skin, with relevance not only to reindeer, but also mouse and human systems.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Vir: Osebne bibliografije
in: SICRIS
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