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Publication : Deregulated expression of c-Myc depletes epidermal stem cells.

First Author  Waikel RL Year  2001
Journal  Nat Genet Volume  28
Issue  2 Pages  165-8
PubMed ID  11381265 Mgi Jnum  J:69795
Mgi Id  MGI:2135447 Doi  10.1038/88889
Citation  Waikel RL, et al. (2001) Deregulated expression of c-Myc depletes epidermal stem cells. Nat Genet 28(2):165-8
abstractText  The beta-catenin/TCF signaling pathway is essential for the maintenance of epithelial stem cells in the small intestine. c-Myc a downstream target of beta-catenin/TCF (ref. 2), can induce differentiation of epidermal stem cells in vitro. 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 beta1 integrin, which is preferentially expressed in epidermal stem cells 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 beta1 integrin expression, which is essential to both keratinocyte migration and stem cell maintenance.
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