173 Hair Follicle Stem Cells: Past, Present, and Future.

1Robert M. Lavker and 2Tung-Tien Sun, Depts. of Dermatology, 1Univ. of Pennsylvania Med. Sch., Philadelphia, PA; 2New York Univ. Med. Sch., New York, NY.

The issue of keratinocyte stem cells is of central importance in epidermal homeostasis, wound repair, and carcinogenesis. One of the most accepted means to identify keratinocyte stem cells takes advantage of the fact that they are normally rarely cycling in vivo, and can be detected experimentally as the “labelretaining cells” (LRCs). When this approach was used to localize the rarely cycling cells of the hair follicle, all of the follicular LRCs were exclusively confined to the bulge – the part of the outer root sheath marking the lowest point of the upper, permanent portion of the follicle. Although it was customarily thought that the hair follicle and the epidermis were governed by separate populations of stem cells, it was puzzling that (1) very few such LRCs were found in the interfollicular epidermis and (2) interfollicular human epidermal cells had less in vitro proliferative potential than the upper follicular epithelial cells. We showed recently that the bulge stem cells give rise not only to the lower follicle, but also to young transit amplifying cells that migrate into normal newborn mouse epidermis as well as wounded adult mouse skin. This provides the first evidence that that the bulge represents a major repository of skin keratinocyte stem cells that may be bipotent as they can give rise to not only the hair follicle, but also to the epidermis. This finding has major implications on hair biology, the long-term maintenance of the epidermis, the pathogenesis of skin carcinomas, and the mechanism and regulation of skin wound repair.