A review: the location, molecular characterisation and multipotency of hair follicle epidermal stem cells.

INTRODUCTION Recent work has focused on the hair follicle as the main repository of multipotent stem cells in skin, which is a neat model to study the mechanisms regulating the proliferation, migration and final fate of adult stem cells. This review examines the available literature for its location, molecular markers and multipotency. METHODS Peer-reviewed journals and monographs on the subject were covered. RESULTS With the application of stem cell-labelling techniques and clonogenicity assay, it is clear that most of the hair follicle stem cells are located at the bulge region, but the base of the hair follicle does contain some clonogenic cells; whether they are stem cells is still unknown. Extensive works have been done in identifying hair follicle stem cells. The potential markers for hair follicle stem cells include: b1-integrin, keratin 19, a6- integrin, CD71, p63, and CD34. Most of these markers are expressed in high levels in hair follicle stem cells, but there is still difficulty in distinguishing hair follicle stem cells from their transitamplifying progeny, and the sorted hair follicle stem cells with these markers are far from pure. As hair follicle stem cells might have been activated after leaving the stem cell niche, the markers for cells in vitro might not be identical to those in vivo. Using double-labelling techniques with BrdU and 3H-Thymidine, and the creation of novel chimera transgenic mice, it was proved that hair follicle stem cells can repopulate wound epidermis, forming epidermis, hair follicles and sebaceous glands, but it contributes little to the epidermis in physiological condition, except the hair follicle. CONCLUSIONS Slow cycling, label-retaining cells exist at the bulge of the hair follicle, with high proliferative potential and clonogenicity. The putative bulge stem cells can contribute to the epidermis, outer root sheath, inner root sheath, hair shaft and sebaceous gland. However, they still lack certain markers to distinguish bulge stem cells from their progeny, and much work needs to focus on the interrelations between bulge cells and interfollicular keratinocyte stem cells, the relations between bulge cells and dermal papilla mesenchyme cells, and the mechanism of hair growth.