Stem cells in the hair follicle bulge contribute to wound repair but not to homeostasis of the epidermis
Stem cells in the hair follicle bulge contribute to wound repair but not to homeostasis of the epidermis
复制标题
DOI：
10.1038/nm1328
复制
发表时间：
2005-12-01
期刊：
影响因子：
82.9
通讯作者：
Cotsarelis, G
中科院分区：
文献类型：
--
作者：
Ito, M;Liu, YP;Cotsarelis, G
在毛囊的隆突区域发现了长寿的上皮干细胞，这导致了表皮更新和受伤后的表皮修复都依赖于这些细胞的假设（1）。为了确定隆突细胞是否是表皮更新所必需的，在此我们通过使用角蛋白1-15（Krt 115）启动子用编码单纯疱疹病毒胸苷激酶（HSV-TK）的自杀基因靶向这些细胞来消融这些细胞（2）。我们表明，消融导致毛囊的完全丧失，但表皮的生存。通过命运映射实验，我们发现毛囊隆起中的干细胞通常不会像以前预测的那样为表皮贡献细胞，表皮组织成表皮增殖单位（3，4）。然而，在表皮损伤后，来自隆突的细胞被募集到表皮中，并以线性方式向伤口中心迁移，最终形成明显的放射状图案。值得注意的是，虽然隆突来源的细胞获得了表皮表型，但大多数细胞在几周内从表皮中消除，表明隆突干细胞通过产生负责急性伤口修复的短寿命“瞬时扩增”细胞对表皮创伤迅速作出反应。我们的发现对基因治疗和开发伤口治疗都有意义，因为有必要将表皮干细胞和毛囊干细胞视为不同的群体。
The discovery of long-lived epithelial stem cells in the bulge region of the hair follicle led to the hypothesis that epidermal renewal and epidermal repair after wounding both depend on these cells(1). To determine whether bulge cells are necessary for epidermal renewal, here we have ablated these cells by targeting them with a suicide gene encoding herpes simplex virus thymidine kinase (HSV-TK) using a Keratin 1-15 (Krt115) promoter(2). We show that ablation leads to complete loss of hair follicles but survival of the epidermis. Through fate-mapping experiments, we find that stem cells in the hair follicle bulge do not normally contribute cells to the epidermis which is organized into epidermal proliferative units, as previously predicted(3,4). After epidermal injury, however, cells from the bulge are recruited into the epidermis and migrate in a linear manner toward the center of the wound, ultimately forming a marked radial pattern. Notably, although the bulgederived cells acquire an epidermal phenotype, most are eliminated from the epidermis over several weeks, indicating that bulge stem cells respond rapidly to epidermal wounding by generating short-lived 'transient amplifying' cells responsible for acute wound repair. Our findings have implications for both gene therapy and developing treatments for wounds because it will be necessary to consider epidermal and hair follicle stem cells as distinct populations.