Research Laboratories, Nippon Menard Cosmetic Co., Ltd, Nagoya, Japan.
Department of Applied Cell and Regenerative Medicine, Fujita Health University School of Medicine, Toyoake, Japan.
J Dermatol. 2018 Dec;45(12):1403-1410. doi: 10.1111/1346-8138.14678. Epub 2018 Oct 15.
Hair follicle stem cells (HFSC) are localized in the bulge region of the hair follicle and play a role in producing hair. Recently, it has been shown that the number of HFSC decreases with age, which is thought to be a cause of senile alopecia. Therefore, maintaining HFSC may be key for the prevention of age-related hair loss, but the regulatory mechanisms of HFSC and the effects of aging on them are largely unknown. In general, stem cells are known to require regulatory factors in the pericellular microenvironment, termed the stem cell niche, to maintain their cell function. In this study, we focused on the extracellular matrix proteoglycan decorin (DCN) as a candidate factor for maintaining the human HFSC niche. Gene expression analysis showed that DCN was highly expressed in the bulge region. We observed decreases in DCN expression as well as the number of KRT15-positive HFSC with age. In vitro experiments with human plucked hair-derived HFSC revealed that HFSC lost their undifferentiated state with increasing passages, and prior to this change a decrease in DCN expression was observed. Furthermore, knockdown of DCN promoted HFSC differentiation. In contrast, when HFSC were cultured on DCN-coated plates, they showed an even more undifferentiated state. From these results, as a novel mechanism for maintaining HFSC, it was suggested that DCN functions as a stem cell niche component, and that the deficit of HFSC maintenance caused by a reduction in DCN expression could be a cause of age-related hair loss.
毛囊干细胞(HFSC)位于毛囊的隆起区域,在产生毛发方面发挥作用。最近,已经表明 HFSC 的数量随着年龄的增长而减少,这被认为是老年性脱发的原因。因此,维持 HFSC 可能是预防与年龄相关的脱发的关键,但 HFSC 的调节机制及其对衰老的影响在很大程度上是未知的。通常,干细胞被认为需要细胞外基质蛋白聚糖核心蛋白聚糖(DCN)等细胞周围微环境中的调节因子,即干细胞龛,以维持其细胞功能。在这项研究中,我们专注于细胞外基质蛋白聚糖核心蛋白聚糖(DCN)作为维持人类 HFSC 龛的候选因子。基因表达分析表明,DCN 在隆起区域中高度表达。我们观察到随着年龄的增长,DCN 的表达以及 KRT15 阳性 HFSC 的数量减少。体外实验中,用人拔出的头发来源的 HFSC 表明,HFSC 在传代过程中失去了未分化状态,并且在此变化之前观察到 DCN 表达的减少。此外,DCN 的敲低促进了 HFSC 的分化。相比之下,当 HFSC 在 DCN 包被的平板上培养时,它们表现出更加未分化的状态。从这些结果中,作为维持 HFSC 的新机制,表明 DCN 作为干细胞龛的组成部分发挥作用,并且 DCN 表达减少导致的 HFSC 维持不足可能是与年龄相关的脱发的原因。