The dermal sheath: An emerging component of the hair follicle stem cell niche

Abstract

Hair follicles cyclically regenerate throughout adult mammalian life, owing to a resident population of epithelial hair follicle stem cells. Stem cell (SC) activity drives bouts of follicle growth, which are periodically interrupted by follicle regression and rest. These phases and the transitions between them are tightly spatiotemporally coordinated by signalling crosstalk between stem/progenitor cells and the various cell types of the microenvironment, or niche. The dermal papilla (DP) is a cluster of specialized mesenchymal cells that have long been recognized for important niche roles in regulating hair follicle SC activation, as well as progenitor proliferation and differentiation during follicle growth. In addition to the DP, the mesenchyme of the murine pelage follicle is also comprised of a follicle-lining smooth muscle known as the dermal sheath (DS), which has been far less studied than the DP yet may be equally specialized and important for hair cycling. In this review, we define the murine pelage DS in comparison with human DS and discuss recent work that highlights the emergent importance of the DS in the hair follicle SC niche. Last, we examine potential therapeutic applications for the DS in hair regeneration and wound healing.

Skin organoids: A new human model for developmental and translational research

“…Although the role of developmental signalling cues have been extensively studied in mice, few of these studies have been directly investigated in developing human skin. In addition to investigations of chemical signalling messengers, future work could elucidate the role of mechanical forces, such as dermis induced constriction forces, on human skin development in the organoid model 15,42‐45 …”

“…In addition to investigations of chemical signalling messengers, future work could elucidate the role of mechanical forces, such as dermis induced constriction forces, on human skin development in the organoid model. 15,[42][43][44][45] Positional patterning is another aspect of embryonic development reflected in skin organoid cultures. The human body contains a variety of skin types, specialized to anatomical locations (eg hairless glabrous skin on the palms).…”

Skin stem cells in health and in disease

“…56 Work by the Biernaskie lab further showed that the sheath itself harbours stem cells that-alongside with HFSC regeneration of the follicle-expand to replenish the dermal sheath and contribute to the dermal papilla of the re-growing anagen follicle. 57 Martino et al 58 in this issue provide a comprehensive review for this emerging niche cell type that regulates follicle regression in the hair cycle and may also serve to directly signal to progenitors and HFSCs to fulfil their functions.…”

Hair follicle stem cells as a skin‐organizing signaling center during adult homeostasis

“…Right above the bulge is the sebaceous gland filled with sebocytes that release the sebum into the hair canal spanning the skin surface (Niemann & Horsley, 2012). The hair follicle is closely surrounded by the dermal sheath, a population of specialized fibroblast with a recently uncovered contractile function, important for hair follicle regression (Martino et al, 2021). Below the hair germ, there is a ball of mesenchymal cells that is known as the dermal papilla (DP), with known relevance to HFSC activation at the telogen‐to‐anagen transition (Morgan, 2014; Chen et al, 2020).…”

“…In addition to the DP, another mesenchymal lineage closely associated with the hair follicle is the dermal sheath that encloses the DP at telogen and the hair follicle at anagen and catagen (Yang & Cotsarelis, 2010; Martino et al, 2021). Recent work demonstrated that the dermal sheath is made of cells with smooth muscle characteristics that contract to draw the DP upwards to bring it closer to the HFSCs, thus ensuring matrix cell apoptosis and proper hair cycle progression (Heitman et al, 2020).…”