Department of Dermatology, Kligman Laboratories, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
J Clin Invest. 2011 Feb;121(2):613-22. doi: 10.1172/JCI44478. Epub 2011 Jan 4.
Androgenetic alopecia (AGA), also known as common baldness, is characterized by a marked decrease in hair follicle size, which could be related to the loss of hair follicle stem or progenitor cells. To test this hypothesis, we analyzed bald and non-bald scalp from AGA individuals for the presence of hair follicle stem and progenitor cells. Cells expressing cytokeratin15 (KRT15), CD200, CD34, and integrin, α6 (ITGA6) were quantitated via flow cytometry. High levels of KRT15 expression correlated with stem cell properties of small cell size and quiescence. These KRT15(hi) stem cells were maintained in bald scalp samples. However, CD200(hi)ITGA6(hi) and CD34(hi) cell populations--which both possessed a progenitor phenotype, in that they localized closely to the stem cell-rich bulge area but were larger and more proliferative than the KRT15(hi) stem cells--were markedly diminished. In functional assays, analogous CD200(hi)Itga6(hi) cells from murine hair follicles were multipotent and generated new hair follicles in skin reconstitution assays. These findings support the notion that a defect in conversion of hair follicle stem cells to progenitor cells plays a role in the pathogenesis of AGA.
雄激素性脱发(AGA),又称普通脱发,其特征是毛囊明显缩小,这可能与毛囊干细胞或祖细胞的丧失有关。为了验证这一假说,我们分析了 AGA 患者脱发和非脱发头皮中毛囊干细胞和祖细胞的存在情况。通过流式细胞术定量分析表达细胞角蛋白 15(KRT15)、CD200、CD34 和整合素,α6(ITGA6)的细胞。高水平的 KRT15 表达与小细胞大小和静止期的干细胞特性相关。这些 KRT15(高)干细胞在脱发头皮样本中得以维持。然而,CD200(高)ITGA6(高)和 CD34(高)细胞群——它们都具有祖细胞表型,因为它们紧密定位于富含干细胞的隆起区,但比 KRT15(高)干细胞更大且更具增殖性——明显减少。在功能测定中,来自小鼠毛囊的类似 CD200(高)Itga6(高)细胞具有多能性,并在皮肤重建测定中产生新的毛囊。这些发现支持这样一种观点,即毛囊干细胞向祖细胞转化的缺陷在 AGA 的发病机制中起作用。