Project description:Wound Induced Hair Follicle neogenesis (WIHN) is a hair neogenesis phenomenon which occurred in the center of scar. Neonatal hair follicle are separated from the preexisting follicles by a hairless circular. We analysed the differentially expressed proteins between inner and outer area of scar at post-wound day 15 by iTRAQ technology.
Project description:The full complement of hair follicles is generated during embryogenesis. Normally, no new hair is created after this time. Large full thickness skin excision wounding can result in the generation of new hair in the adult. Placodes can be observed following complete reepithelialization at wound day 14. The events leading to hair neogenesis following wounding remain poorly understood. Late healing events (from wound day 10 to wound day 14) provide a possible window of induction for hair regeneration. We used microarrays to analyse changes in gene expression during late skin healing to provide candidates for factors involved in hair neogenesis following wounding. 6 week old C57Bl/6 mice received large full thickness skin excisions. Healing wound tissue was excised at wound day 10, 12 or 14 and analyzed for gene expression.
Project description:The full complement of hair follicles is generated during embryogenesis. Normally, no new hair is created after this time. Large full thickness skin excision wounding can result in the generation of new hair in the adult. Placodes can be observed following complete reepithelialization at wound day 14. The events leading to hair neogenesis following wounding remain poorly understood. Late healing events (from wound day 10 to wound day 14) provide a possible window of induction for hair regeneration. We used microarrays to analyse changes in gene expression during late skin healing to provide candidates for factors involved in hair neogenesis following wounding.
Project description:Mice were wounded and measured for regeneration starting 4 days after wound closure with simultaneous measurement of hair follicle neogenesis and biopsing. At each time point, RNA was collected from one mouse with high number of regenerated follicles and one without regenerated follicles. Whole skin biopsies of wound scars were submitted for Affymetrix Exon arrays. 3 replicates of mice with high number of regenerated follicles, 3 replicates of mice with no regenerated follicles; each pair taken at a different date after wound closure.
Project description:Tissue regeneration is a process that recapitulates the molecular and mechanical aspects of development and evolution. We use the wound-induced hair neogenesis (WIHN) model to investigate the mechanical and molecular responses of the laboratory (Mus) and African spiny (Acomys) mice. Laboratory and spiny mice showed an opposite trend of spatiotemporal morphogenetic field for WIHN during wound healing, and wound stiffness gradient across the whole wound bed predicated pattern of hair formation. Using bulk and single-cell RNA-seq analysis and K14-Cre-Twist1 transgenic mice, we identified the central role of the Twist1 pathway as the mediator of epidermal-dermal interaction and the emergence of periodic hair primordia. Lastly, we generated a Turing model with an underlying measure of stiffness to support a two-scale tissue mechanic model to explain the setup of a morphogenetic field from a wound bed (mm scale) or periodically arranged hair primordia from a morphogenetic field (μm scale). Delineating the common and distinct chemo-mechanical events during regenerative wound healing between laboratory and African spiny mice reveal its evo-devo advantages, which provide new perspectives for regenerative medicine.
Project description:Tissue regeneration is a process that recapitulates the molecular and mechanical aspects of development and evolution. We use the wound-induced hair neogenesis (WIHN) model to investigate the mechanical and molecular responses of the laboratory (Mus) and African spiny (Acomys) mice. Laboratory and spiny mice showed an opposite trend of spatiotemporal morphogenetic field for WIHN during wound healing, and wound stiffness gradient across the whole wound bed predicated pattern of hair formation. Using bulk and single-cell RNA-seq analysis and K14-Cre-Twist1 transgenic mice, we identified the central role of the Twist1 pathway as the mediator of epidermal-dermal interaction and the emergence of periodic hair primordia. Lastly, we generated a Turing model with an underlying measure of stiffness to support a two-scale tissue mechanic model to explain the setup of a morphogenetic field from a wound bed (mm scale) or periodically arranged hair primordia from a morphogenetic field (μm scale). Delineating the common and distinct chemo-mechanical events during regenerative wound healing between laboratory and African spiny mice reveal its evo-devo advantages, which provide new perspectives for regenerative medicine.
Project description:Human and murine skin wounding commonly result in fibrotic scarring but the murine wounding model Wound Induced Hair Neogenesis (WIHN) can frequently result in a regenerative repair response. Here we show in single cell RNA-seq comparisons of semi-regenerative and fibrotic WIHN wounds, increased expression of phagocytic/lysosomal genes in macrophages associated with predominance of fibrotic myofibroblasts in fibrotic wounds. Investigation revealed that macrophages in the late wound drive fibrosis by phagocytizing dermal Wnt inhibitor SFRP4 to establish persistent Wnt activity. In accordance, phagocytosis abrogation resulted in transient Wnt activity and a more regenerative healing. Phagocytosis of SFRP4 was integrin-mediated and dependent on the interaction of SFRP4 with the EDA splice variant of fibronectin. In the human skin condition Hidradenitis suppurativa, phagocytosis of SFRP4 by macrophages correlated with fibrotic wound repair. These results reveal that macrophages can modulate a key signaling pathway via phagocytosis to alter the skin wound healing fate.
Project description:Mice were wounded and measured for regeneration starting 4 days after wound closure with simultaneous measurement of hair follicle neogenesis and biopsing. At each time point, RNA was collected from one mouse with high number of regenerated follicles and one without regenerated follicles.