Diverse cellular players orchestrate regeneration after wounding

Abstract

Fibrosis is one of the largest sources of human morbidity. The skin is a complex organ where interplay between diverse cell types and signalling pathways is essential both in homeostasis and wound repair, which can result in fibrosis or regeneration. This makes skin a useful model to study fibrosis and regeneration. While fibrosis often occurs postinjury, both clinical and laboratory observations suggest skin regeneration, complete with reconstituted cell diversity and de novo hair follicles, is possible.Extensive research performed in pursuit of skin regeneration has elucidated the key players, both cellular and molecular. Interestingly, some cells known for their homeostatic function are not implicated in regeneration or wound-induced hair neogenesis (WIHN), suggesting regeneration harnesses separate functional pathways from embryogenesis or other non-homeostatic mechanisms. For example, classic bulge cells, noted for their role in normally cycling hair follicles, do not finally contribute to long-lived cells in the regenerated tissue. During healing, multiple populations of cells, among them specific epithelial lineages, mesenchymal cells, and immune cells promote regenerative outcomes in the wounded skin. Ultimately, targeting specific populations of cells will be essential in manipulating a postwound environment to favour regeneration in lieu of fibrosis.

More than just bricks and mortar: Fibroblasts and ECM in skin health and disease

“…Wound size is highly relevant to healing outcomes, because in adult mice only wounds that are larger that 1 cm 2 repair by regenerating new hair follicles 27 and new adipocytes 28 in their centre. This regenerative phenomenon, also known as wound‐induced hair follicle neogenesis (WIHN) 29,30 is highly desirable, yet normally not achievable clinically and variable across species, being prominent in spiny mice 31,32 and deficient in rats 33 and pigs 34 . Cellular heterogeneity in the WIHN model has been recently studied using scRNA‐seq 35–39 .…”

Skin stem cells in health and in disease

“…6,9,84 Moreover, while wounds that heal from full thickness injury (the type of injury affecting both the epithelium and dermis) often lack hair follicles, recent findings suggest that some hair follicle structures can form de novo from the healed epidermis and dermis in large-size wounds. In this issue, Williams and Garza 85…”

“…Moreover, while wounds that heal from full thickness injury (the type of injury affecting both the epithelium and dermis) often lack hair follicles, recent findings suggest that some hair follicle structures can form de novo from the healed epidermis and dermis in large‐size wounds. In this issue, Williams and Garza 85 provide an up‐to‐date review on wound healing and how different skin epithelial, mesenchymal and immune cell populations participate in the process. Huang et al 31 demonstrate the process by which hair follicles repair themselves after chemotherapy‐induced injury.…”

Regulation of WOX11 Expression Represents the Difference Between Direct and Indirect Shoot Regeneration

“…High ratios of auxin to cytokinin induced root formation, whereas low ratios of auxin and cytokinin led to shoot regeneration (Skoog and Miller, 1957). De novo organogenesis is the prerequisite of micropropagation and genetic transformation, and provide an important system for studying fundamental biological questions (Sang et al, 2018a;Williams and Garza, 2021).…”