Wound Induced Hair Neogenesis - A Novel Paradigm for Studying Regeneration and Aging

Abstract

Hair follicles are the signature dermal appendage of mammals. They can be thought of as mini-organs with defined polarity, distinct constituent cell types, dedicated neurovascular supply, and specific stem cell compartments. Strikingly, some mammals show a capacity for adult hair follicle regeneration in a phenomenon known as wound-induced hair neogenesis (WIHN). In WIHN functional hair follicles reemerge during healing of large cutaneous wounds, and they can be counted to provide an index of regeneration. While age-related decline in hair follicle number and cycling are widely appreciated in normal physiology, it is less clear whether hair follicle regeneration also diminishes with age. WIHN provides an extraordinary quantitative system to address questions of mammalian regeneration and aging. Here we review cellular and molecular underpinnings of WIHN, explore known age-related changes to these elements, and present unanswered questions for future exploration.

Keywords: STAT3; Wnt; aging; hair follicle neogenesis; hair follicle stem cells; regeneration; wound-induced hair follicle neogenesis.

FIGURE 1

Major signal transduction pathways involved in WIHN. Circles indicate mediators known to have age-related changes. Young adult mice with high wnt/β-catenin levels in the dermis had fewer pro-regenerative fibroblasts and impaired WIHN (Rognoni et al., 2016). IL-6 levels are lower in aged mouse skin with impaired wound healing (Keyes et al., 2016), and low IL-6/STAT-3 is also observed in mice with low WIHN (Nelson et al., 2015). Shh signaling is a major driver of developmental and regenerative hair follicle morphogenesis. Age-related changes in Shh during WIHN have not been demonstrated.