Project description:Skin has distinct characteristics depending on the anatomical site; however, the cell and molecular differences, and their functional implications, have been little described. RNA-sequencing of healthy adult mouse skin from the abdomen, back, and face/cheek has revealed that dermis from different sites is distinct, and that this aligns with their diverse embryonic origins (abdominal dermis develops from lateral plate mesoderm, dorsal dermis from paraxial mesoderm, and cheek dermis from neural crest). The functional implications for wound repair are evident from the differences in extracellular matrix and cell migration observed in tissue and dermal fibroblasts from these sites, and the histological and transcriptional variations during a wound response.
Project description:Preservation of the denatured dermis can facilitate wound repair as well as restore hand function.Denatured dermis can be reversibly recovered after deep partial thermal injury. In this dataset, we include the m6A methylated RNA data obtained from normal skin tissues (C group) and denatured dermis (T group).
Project description:The expression profile during wound repair of cutaneous excisional wound (2x2 cm) was studied. The tissue was sampled from the centre of the open wound (day 3/7/14) or centre of the wound scar (day 21/35/70). The microarray slide were scanned in low intensity scan and high intensity scan mode. Wound tissue (day 3, day 7, day 14, day 21, day 35, day 70, n = 4 per interval) vs. control - uninjured skin (day 0, n=4 ). In each interval two biological replicates of four were labeled with flip dyes.
Project description:The expression profile during wound repair of cutaneous excisional wound (2x2 cm) was studied. The tissue was sampled from the centre of the open wound (day 3/7/14) or centre of the wound scar (day 21/35/70). The microarray slide were scanned in low intensity scan and high intensity scan mode.
Project description:Non-healing wounds are a major area of unmet clinical need that remain problematic to treat; therefore, improved understanding of pro-healing mechanisms is invaluable. The enzyme arginase1 is involved in pro-healing responses with its role in macrophages best-characterised. Arginase1 is also expressed by keratinocytes; however, the function of arginase1 in these critical wound repair cells is not understood. We characterised arginase1 expression in keratinocytes during normal cutaneous repair and reveal de novo temporal and spatial expression at the epidermal wound edge. Interestingly, epidermal arginase1 expression was decreased in both human and murine delayed healing wounds. We, therefore, generated a keratinocyte specific arginase1-null mouse model (K14-cre;Arg1fl/fl) to explore arginase function. Wound repair, linked to changes in keratinocyte proliferation, migration and differentiation, was significantly delayed in K14-cre;Arg1fl/flmice. Gene expression was studied by microarray.
Project description:Our knowledge of transcriptional heterogeneities in epithelial stem/progenitor cell compartments is limited. Epidermal basal cells sustain cutaneous tissue maintenance and drive wound healing. Previous studies have probed basal cell heterogeneity in stem/progenitor potential, but a comprehensive dissection of basal cell dynamics during differentiation is lacking. Using single-cell RNA-sequencing coupled with RNAScope and fluorescence lifetime imaging, we identify three non-proliferative and one proliferative basal cell transcriptional states in homeostatic skin that differ in metabolic preference and become spatially partitioned during wound re-epithelialization. Pseudotemporal trajectory and RNA velocity analyses produce a quasi-linear differentiation hierarchy where basal cells progress from Col17a1high/Trp63high state to early response state, proliferate at the juncture of these two states, or become growth arrested before differentiating into spinous cells. Wound healing induces plasticity manifested by dynamic basal-spinous interconversions at multiple basal states. Our study provides a systematic view of epidermal cellular dynamics supporting a revised “hierarchical-lineage” model of homeostasis.
Project description:Tissue repair processes maintain proper organ function following mechanical or infection related damage. In addition to anti-bacterial properties, MAIT cells express a tissue repair transcriptomic program and promote skin wound healing when expanded. Herein, we use a human‑like full‑thickness skin excision mouse model to assess the underlying mechanisms of MAIT cell tissue repair function. Single-cell RNAseq analysis suggests that skin MAIT cells already express a repair program at steady state. Following skin excision, MAIT cells promote keratinocyte proliferation thereby accelerating healing. Using skin grafts, parabiosis and adoptive transfer experiments, we show that MAIT cells migrate into the wound from other tissues in a TCR independent but CXCR6 dependent manner. Amphiregulin secreted by MAIT cells following excision promotes wound healing. The repair function is independent of sustained TCR stimulation. Overall, our study provides mechanistic insight into MAIT cell wound healing function in the skin.
Project description:Skin scarring following dermal injury causes extreme pain and pschological trauma for patients. Currently, we do not have effective treatments to prevent or reverse skin scarring. Fibroblast heterogeneity has been shown within the unwounded mouse dorsal dermis, with fibroblast subpopulations being identified according to anatomical location and embryonic lineage. Using RNA-sequencing and single cell RNA sequencing, we demonstrate that Prrx1-expressing mouse fibroblasts are responsible for acute and chronic scaring in the ventral mouse dermis. In summary, we have identified and characterized a fibroblast subpopulation in the mouse ventral dermis with intrinsic scar-forming potential.