Liu Yaping, Lyle Stephen, Yang Zaixin, Cotsarelis George
Department of Dermatology, Kligman Laboratories, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
J Invest Dermatol. 2003 Nov;121(5):963-8. doi: 10.1046/j.1523-1747.2003.12600.x.
Putative epithelial stem cells in the hair follicle bulge are thought to play pivotal roles in the homeostasis, aging, and carcinogenesis of the cutaneous epithelium. Elucidating the role of bulge cells in these processes has been hampered by the lack of gene promoters that target this area with specificity. Here we describe the isolation of the mouse keratin 15 (K15) promoter and demonstrate its utility for preferentially targeting hair follicle bulge cells in adult K15/lacZ transgenic mice. We found that patterns of K15 expression and promoter activity changed with age and correlated with levels of differentiation within the cutaneous epithelium; less differentiated keratinocytes in the epidermis of the neonatal mouse and in the bulge area of the adult mouse preferentially expressed K15. These findings demonstrate the utility of the K15 promoter for targeting epithelial stem cells in the hair follicle bulge and set the stage for elucidating the role of bulge cells in skin biology.
毛囊隆突部的假定上皮干细胞被认为在皮肤上皮的稳态、衰老及致癌过程中发挥关键作用。由于缺乏能特异性靶向该区域的基因启动子，阐明隆突细胞在这些过程中的作用受到了阻碍。在此，我们描述了小鼠角蛋白15（K15）启动子的分离，并证明了其在成年K15/lacZ转基因小鼠中优先靶向毛囊隆突细胞的效用。我们发现，K15的表达模式和启动子活性随年龄变化，并与皮肤上皮内的分化水平相关；新生小鼠表皮和成年小鼠隆突区域中分化程度较低的角质形成细胞优先表达K15。这些发现证明了K15启动子在靶向毛囊隆突部上皮干细胞方面的效用，并为阐明隆突细胞在皮肤生物学中的作用奠定了基础。
