Epigenetic control of skin and hair regeneration after wounding

Abstract

Skin wound healing is a complex regenerative phenomenon that can result in hair follicle neogenesis. Skin regeneration requires significant contribution from the immune system and involves substantial remodeling of both epidermal and dermal compartments. In this viewpoint, we consider epigenetic regulation of reepithelialization, dermal restructuring and hair neogenesis. Because little is known about the epigenetic control of these events, we have drawn upon recent epigenetic mapping and functional studies of homeostatic skin maintenance, epithelial-mesenchymal transition in cancer, and new works on regenerative dermal cell lineages and the epigenetic events that may shape their conversion into myofibroblasts. Finally, we speculate on how these various healing components might converge for wound-induced hair follicle neogenesis.

Epigenetic control in skin development, homeostasis and injury repair

“…This provides an opportunity for future broader clinical implementation of epigenetic targeting drugs for wound healing and treatment of skin disease. Thus, manipulating levels of histone modifications in adult tissue SCs in vivo for possible control of tissue regeneration is an important and timely endeavour . Furthermore, skin is a valuable model to study the behaviour of adult SCs.…”

“…In vitro scratch assays of cultured keratinocyte revealed that JMJD3 interacts with NF‐κB to demethylate H3K27me3 at the promoter of inflammatory, matrix metalloproteinase and growth factor genes . Interestingly, basal cell migration to the wounds resembles malignant cancer formation, which occurs by epithelial–mesenchymal transition (EMT) . One of the well‐known EMT regulators Slug/Snail2 was shown to be upregulated in the wounded skin .…”

“…Skin punch wound is a widely studied injury model to investigate contribution of different SC populations in skin repair. Wound healing includes several distinct processes, such as inflammation, re‐epithelialization and dermis reorganization . Several recent studies have highlighted the roles of histone modifiers in re‐writing the epigenetic identity during wound‐induced re‐epithelization.…”

Inflammation markers in cutaneous melanoma - edgy biomarkers for prognosis

“…Epithelial-mesenchymal transition (EMT) is a recent reported process through which epithelial cells lose some of their innate characteristics (cell polarity and cell-cell adhesion) and are endowed with migratory and invasive properties becoming mesenchymal stem cells 15 . Wound healing has remarkable similarities to cancer in EMT induction 16 . During wound re-epithelialization epidermal keratinocytes, acquire migratory phenotypes 17 .…”

Understanding skin morphogenesis across developmental, regenerative and evolutionary levels

“…Wound‐induced regeneration is thought to be controlled by a complex signalling and epigenetic mechanism . In this issue, Garza's and Tumbar's groups discuss the roles of non‐coding double‐stranded RNAs and epigenetic reprogramming, respectively, in enabling such regenerative behaviour.…”