Keratin 15 promoter targets putative epithelial stem cells in the hair follicle bulge

Keratin 15 promoter targets putative epithelial stem cells in the hair follicle bulge
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DOI:
10.1046/j.1523-1747.2003.12600.x
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发表时间:
2003-11-01
影响因子:
6.5
通讯作者:
Cotsarelis, G
Cotsarelis, G
中科院分区:
医学1区
文献类型:
--
作者:
Liu, YP;Lyle, S;Cotsarelis, G

文献摘要

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毛囊隆突中的上皮干细胞被认为在皮肤上皮的稳态、衰老和癌变中起关键作用。由于缺乏特异性靶向这一区域的基因启动子,阐明隆突细胞在这些过程中的作用受到阻碍。在这里,我们描述了小鼠角蛋白15(K15)启动子的分离,并证明其效用,优先针对毛囊隆突细胞在成年K15/lacZ转基因小鼠。我们发现,K15的表达和启动子活性的模式随着年龄的变化,并与皮肤上皮内的分化水平;分化程度较低的角质形成细胞在新生小鼠的表皮和成年小鼠的隆起区优先表达K15。这些发现证明了K15启动子在毛囊隆突中靶向上皮干细胞的效用,并为阐明隆突细胞在皮肤生物学中的作用奠定了基础。
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.