Chapter 2 53 Unless the skin is injured, bulge stem cells exclusively contribute to hair follicle maintenance and regeneration, despite the fact that they are also capable of generating sebaceous glands and the interfollicular epidermis. Conversely, at least in mice, epithelial cells may assume the role of hair follicle stem cells under certain wounding conditions, which may lead to hair follicle neogenesis in wounded skin.57 On the other hand, it has also been demonstrated that bulge epithelial stem cells can also contribute to wound repair.58 The long life span also exposes epithelial stem cells to deadly environmental exposures, and their quiescent character may facilitate retention of carcinogenesis, thus rendering them more susceptible to tumor development, such as basal cell carcinoma. Hair Pigmentation Most mammals are covered with a coat of pigmented hair. Hair pigmentation serves multiple purposes, including skin protection against UV irradiation, thermoregulation, camouflage, and sexual signaling.59 The color variants of mammalian hair, including spotting and albinism, are the result of melanocyte activity and have been shown to be determined by the action of multiple genes. Melanocytes inside each follicle are responsible for producing pigment granules, called melanin, for the newly formed hair during each cycle. Although melanocytes and their precursors reside in the hair matrix and along the ORS of anagen hair follicles, only fully differentiated melanocytes, located above and around the DP during anagen, produce melanin in lysosome- related organelles, melanosomes (Figure 5). These melanosomes are actively exported and transferred to the recipient hair shaft keratinocytes, resulting in the formation of a pigmented hair shaft. In human skin, melanocytes are also found in the basal layer of the epidermis to determine the skin color.60 Generally, if more melanin is present, the color of the hair is darker if less melanin is present, the hair is lighter. Melanin is a potent free-radical scavenger and has excellent photo-protection functions. Melanin absorbs harmful UV irradiation and transforms the energy into harmless heat. Therefore,