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Role of bulge cells in wound healing: possible implications for hidradenitis suppurativa
Author(s) -
Ito M.,
Liu Y.,
Yang Z.,
Nguyen J.,
Morris R.,
Liang F.,
Cotsarelis G.
Publication year - 2006
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.0906-6705.2006.0436c.x
Subject(s) - hair follicle , biology , epidermis (zoology) , wound healing , bulge , stem cell , microbiology and biotechnology , endocrinology , anatomy , immunology , stars , physics , astronomy
The hair follicle bulge harbors a cluster of quiescent epithelial stem cells, which generate the new lower hair follicle during follicle cycling. The role of bulge cells for maintenance of the hair follicle and epidermis during normal homeostasis and after wounding remains controversial. To address these questions, we targeted the suicide gene, thymidine kinase (TK), or CrePR recombinase to hair follicle bulge cells using a K15 promoter. Administration of ganciclovir to K15‐TK mice caused their death due to gastrointestinal injury. We then treated immunodeficient mice carrying K15‐TK skin grafts with ganciclovir. This resulted in injury of bulge cells within several days. Loss of hair and permanent injury to hair follicles ensued. Dermal scarring was also present. The epidermis without follicles survived for several months. To further assess the contribution of bulge cells to epidermis, we used double transgenic K15‐crePR1, R26R mice. After 5 days of treatment with RU‐486 (time 0), bulge cells and a small fraction of epidermal cells expressed LacZ under control of the ROSA promoter. To determine whether bulge cells moved into the epidermis under normal homeostatic conditions, we counted labeled epidermal basal cells at times 0, 30 days, and 180 days. We found that the percentage of labeled epidermal basal cells (approximately 1%) remained constant, indicating an absence of cell movement from the bulge to the epidermis. After punch wounding, bulge progeny were detected in a radial pattern in the re‐epithelialized area. Radial streaks of bulge cell progeny emanated from the hair follicles at the wound edge. Bulge cell progeny proliferated and expressed normal epidermal differentiation markers such as keratin 10 and loricrin. Overall, these results indicate that follicular stem cells in the bulge are necessary for hair follicle survival and that these cells functionally contribute to epidermal regeneration in response to wounding; however, the epidermis self‐renews autonomously of the bulge under normal conditions. The role of bulge cells in hidradenitis suppurativa (HS) is not known; however, pathological studies suggest aberrant proliferation of the hair follicle may accompany HS and inappropriate stem cell activation and differentiation could be a component of this disorder. The K15‐crePR1 transgenic mouse will serve as a powerful tool for evaluating the role of hair follicle stem cells in mouse models of HS. Studying hair follicle stem cells with recently defined markers for these cells will be useful for evaluating stem cell behavior in HS lesions.