030 Hair Follicle Stem Cells in Human Skin Development

M. Akiyama. Department of Dermatology, Teikyo University School of Medicine, Ichihara Hospital, Ichihara, Japan

Knowledge of localization and the characteristic features of hair follicle stem cells in developing human hair follicles contributes to a further understanding of the mechanisms underlying human hair follicle morphogenesis. The sequential localization and morphological characteristics of hair follicle stem cells were investigated. In addition, the expression of hemidesmosomal components including laminin 5, ß4 integrin, and type VII collagen were also studied in the stem cell sites during human hair follicle development. Immunohistological observation revealed that ß1 integrin-rich, E-cadherin- and beta- and gamma-catenin-poor cells, possible stem cells, were localized to the entire hair germ (65-84 d estimated gestational age (EGA)) and later to the outermost cells of the hair peg (85-104 d EGA). In the bulbous hair peg (105-135 d EGA) as well as the differentiated lanugo hair follicle (>135 d EGA), these putative stem cells were settled in the bulge and the outermost layer of the outer root sheath. The putative stem cells were also high in EGF receptor expression and positive with keratin 19. Ultrastructural observation of human fetal skin specimens revealed that these â1 integrin-rich, E-cadherin- and beta- and gamma-catenin-poor cells showed similar, undifferentiated morphologic features. In particular, the bulge cells had abundant free ribosomes and glycogen particles, but almost no cytoplasmic organelles indicative of differentiation. Concerning the expression of hemidesmosomal components, positive stainings were continuously observed in the basement membrane zone of the hair germ and the hair peg, although the stainings were weak or negative in the lower portion of the hair peg. In the bulbous hair peg and the differentiated lanugo hair follicle, the hemidesmosomal components were expressed in the basement membrane zone from the interfollicular epidermis to the bulge, and also in the contact area between the matrix cells and the dermal papilla cells. These results support the idea that the human fetal hair follicle bulge is a stem cell site for follicular epithelium from the bulbous hair peg stage and suggest that hemidesmosomal components are continuously expressed in the stem cell sites during hair follicle morphogenesis.