The skin: a home to multiple classes of epithelial progenitor cells

Abstract

To maintain homeostasis in the adult skin, epithelial keratinocyte stem cells are thought to divide infrequently giving rise to short-lived (transit amplifying) cells that undergo a limited number of cell divisions and ultimately terminal differentiation. This model for the epidermal stem cell niche has increased in complexity by the multiple putative progenitor keratinocyte populations that have recently been identified in distinct regions of the interfollicular epidermis and hair follicle appendages. Under normal conditions, these progenitor populations are long-lived and able to sustain the cellular input to certain epidermal structures including the interfollicular epidermis and sebaceous gland. Other putative epithelial progenitors derived from the hair follicle possess high in vitro proliferative capacity and are able to regenerate skin, hair and sebaceous lineages in transplantation studies. These new findings present the cutaneous epithelium as a highly compartmentalized structure potentially maintained by multiple classes of progenitor cells. In this review, we will discuss the implications of these new putative epithelial progenitor populations and their potential to be influenced by external stimuli for skin homeostasis and carcinogenesis.

Figure 1. Landscape of adult murine epidermis showing the multiple compartments of stem and putative progenitor populations

IFE progenitors maintain the proliferative and differentiative compartments of the epidermis. Blimp1⁺ progenitors in the SG maintain the sebocyte pool, and bulge stem cells maintain matrix progenitor cell populations that are committed to hair differentiation. Putative progenitor populations identified as MTS24⁺ cells (between double-hashed lines) or the UI region (between single-hashed lines) reside in the HF above the bulge region. Arrows designate known or unknown (?) progeny derived from each population. Abbreviations: IFE, interfollicular epidermis; SG, sebaceous gland; UI, upper isthmus.