Stem cells in the hair follicle bulge contribute to wound repair but not to homeostasis of the epidermis.
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. 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 (Krt1-15) promoter. 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. 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 bulge-derived 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.
Ito
Mayumi
M
Department of Dermatology, Kligman Laboratories, University of Pennsylvania School of Medicine, M8 Stellar-Chance Building, 422 Curie Boulevard, Philadelphia, Pennsylvania 19104, USA.
Liu
Yaping
Y
Yang
Zaixin
Z
Nguyen
Jane
J
Liang
Fan
F
Morris
Rebecca J
RJ
Cotsarelis
George
G
D000818:Animals; D001973:Bromodeoxyuridine; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D000078404:Epidermal Cells; D004817:Epidermis / Q000293:injuries* / Q000502:physiology*; D015774:Ganciclovir; D041722:Genes, Transgenic, Suicide / Q000235:genetics; D018859:Hair Follicle / Q000166:cytology*; D053569:Keratin-15; D007633:Keratins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic / Q000235:genetics; D018139:Simplexvirus / Q000235:genetics; D013234:Stem Cells / Q000166:cytology*; D013937:Thymidine Kinase / Q000235:genetics; D014945:Wound Healing / Q000502:physiology*; D001616:beta-Galactosidase / Q000378:metabolism
D053569:Keratin-15; C492053:Krt15 protein, mouse; D007633:Keratins; D013937:Thymidine Kinase; D001616:beta-Galactosidase; D001973:Bromodeoxyuridine; D015774:Ganciclovir