New Perspectives on Melanoma_ The Role of PAX3

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Unformatted text preview: cells. Figure 1.1.4. Distribution of three distinct populations of melanocytic cells in human skin. This diagram represents a simplified structure of human skin and associated hair follicle. Two populations of mature differentiated melanocytes are located in the epidermis and in the bulb of the hair follicle. Melanocyte stem cells are located in the bulge region of the hair follicle (adapted from [77]). Adult skin does however contain another population of melanocytic cells, melanocyte stem cells, located in the lower permanent portion of the hair follicle, just below the musculus arrector pili. This stem cell niche (called a ‘bulge’), provides a reservoir of adult stem cells that give rise to new hair [78,79]. Bulge melanocyte stem cells represent a pool of progenitor cells serving to repopulate 9 Chapter I – Thesis Overview lost melanocytes in the hair and presumably in the epidermis [77,80‐82]. Melanocyte stem cells are immature, slow cycling and self‐maintaining cells that remain quiescent in the niche until appropriate external stimuli initiate their proliferation, migration and differentiation [78]. Since the hair and hair follicle go through continuous cycles of loss and regeneration (Figure 1.1.5.), so therefore do follicular melanocytes. During the hair cycle, the upper portion of the hair follicle remains permanent (Figure 1.1.4.), in contrast to the lower transient portion, which undergoes cyclical stages of hair growth andloss. In the anagen phase, the newly formed hair shaft grows and hair protrudes through the skin surface. Following this, during the destructive catagen phase, the lower part of the follicle undergoes apoptosis. The dermal papilla is then brought to rest below the bulge, and after the resting phase (telogen), a critical threshold of activating factors is reached and the bulge stem cells become activated to regrow the hair. During the subsequent early anagen phase, hair follicle regeneration starts from the bulge area, followed by the downward growth of the basal portion of the follicle to form the hair matrix. This is accompanied by simult...
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