Lyle S, Christofidou-Solomidou M, Liu Y, Elder D E, Albelda S, Cotsarelis G
University of Pennsylvania Medical Center, Departments of Pathology and Laboratory Medicine, Medicine and Dermatology, Philadelphia, PA 19104, USA.
J Cell Sci. 1998 Nov;111 ( Pt 21):3179-88. doi: 10.1242/jcs.111.21.3179.
Stem cells are vital for the homeostasis of self-renewing tissues such as the hair follicle. Epithelial stem cells have been implicated in tumorigenesis and wound healing, and their manipulation may have wide ranging applications including gene therapy and tissue transplantation. Rodent hair follicle stem cells have been localized to an area of the follicle called the bulge, however, the identification and characterization of human hair follicle stem cells has been hampered by a lack of cellular markers for this area. We have determined that the C8/144B monoclonal antibody, originally generated against a short intracytoplasmic peptide of CD8, preferentially immunostains hair follicle bulge keratinocytes without staining the remaining hair follicle. Using expression cloning, we identified cytokeratin 15 as the keratinocyte protein recognized by the C8/144B monoclonal antibody. By delineating the bulge using this antibody, we demonstrated that bulge cells possess a stem cell phenotype characterized by their slowly-cycling nature, preferential proliferation at the onset of new hair follicle growth, high level of beta1 integrin expression, and expression of cytokeratin 19.
干细胞对于毛囊等自我更新组织的内环境稳定至关重要。上皮干细胞与肿瘤发生和伤口愈合有关,对其进行操控可能具有广泛应用,包括基因治疗和组织移植。啮齿动物毛囊干细胞已被定位到毛囊的一个称为隆突的区域,然而,人类毛囊干细胞的鉴定和特征描述因该区域缺乏细胞标志物而受到阻碍。我们已确定,最初针对CD8的短胞质内肽产生的C8/144B单克隆抗体,优先免疫染色毛囊隆突角质形成细胞,而不染色其余毛囊。通过表达克隆,我们鉴定出细胞角蛋白15是被C8/144B单克隆抗体识别的角质形成细胞蛋白。通过使用该抗体描绘隆突,我们证明隆突细胞具有干细胞表型,其特征为细胞周期缓慢、在新毛囊生长开始时优先增殖、高水平的β1整合素表达以及细胞角蛋白19的表达。