Nature Genetics
28, 165 - 168 (2001)
doi:10.1038/88889
Deregulated expression of c-Myc depletes epidermal stem cellsRebekah L. Waikel1, Yasuhiro Kawachi1, Patricia A. Waikel1, Xiao-Jing Wang1, 2
& Dennis R. Roop1, 21
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA. 2
Department of Dermatology, Baylor College of Medicine, Houston, Texas 77030, USA.
Correspondence should be addressed to Dennis R. Roop roopd@bcm.tmc.eduThe  -catenin/TCF signaling pathway is essential for the maintenance of epithelial stem cells in the small intestine1. c-Myc a downstream target of -catenin/TCF (ref. 2), can induce differentiation of epidermal stem cells in vitro
3. To determine the role of c-Myc in epidermal stem cells in vivo, we have targeted expression of human MYC2 to the hair follicles and the basal layer of mouse epidermis using a keratin 14 vector (K14.MYC2). Adult K14.MYC2 mice gradually lose their hair and develop spontaneous ulcerated lesions due to a severe impairment in wound healing; their keratinocytes show impaired migration in response to wounding. The expression of 1 integrin, which is preferentially expressed in epidermal stem cells4 is unusually low in the epidermis of K14.MYC2 mice. Label-retaining analysis to identify epidermal stem cells reveals a 75% reduction in the number of stem cells in 3-month-old K14.MYC2 mice, compared with wildtype mice. We conclude that deregulated expression of c-Myc in stem cells reduces 1 integrin expression, which is essential to both keratinocyte migration and stem cell maintenance.
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