title: Hair Follicle Bulge Stem Cells Appear Dispensable for the Acute Phase of Wound Re-epithelialization.
abstract: The cutaneous healing response has evolved to occur rapidly, in order to minimize infection and to re-establish epithelial homeostasis. Rapid healing is achieved through complex coordination of multiple cell types, which importantly includes specific cell populations within the hair follicle (HF). Under physiological conditions, the epithelial compartments of HF and interfollicular epidermis remain discrete, with K15(+ve) bulge stem cells contributing progeny for HF reconstruction during the hair cycle and as a basis for hair shaft production during anagen. Only upon wounding do HF cells migrate from the follicle to contribute to the neo-epidermis. However, the identity of the first-responding cells, and in particular whether this process involves a direct contribution of K15(+ve) bulge cells to the early stage of epidermal wound repair remains unclear. Here we demonstrate that epidermal injury in murine skin does not induce bulge activation during early epidermal wound repair. Specifically, bulge cells of uninjured HFs neither proliferate nor appear to migrate out of the bulge niche upon epidermal wounding. In support of these observations, Diphtheria toxin-mediated partial ablation of K15(+ve) bulge cells fails to delay wound healing. Our data suggest that bulge cells only respond to epidermal wounding during later stages of repair. We discuss that this response may have evolved as a protective safeguarding mechanism against bulge stem cell exhaust and tumorigenesis. Stem Cells 2016;34:1377-1385.
authors.affiliation: The Healing Foundation Centre, Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Clare L
authors.initials: CL
authors.lastname: Garcin
authors.affiliation: The Healing Foundation Centre, Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.|Institute of Inflammation and Repair, University of Manchester, Manchester, United Kingdom.
authors.forename: David M
authors.initials: DM
authors.lastname: Ansell
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Denis J
authors.initials: DJ
authors.lastname: Headon
authors.affiliation: Institute of Inflammation and Repair, University of Manchester, Manchester, United Kingdom.|Department of Dermatology, University of Münster, Münster, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Paus
authors.affiliation: The Healing Foundation Centre, Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Hardman
mesh_terms: D000818:Animals; D017209:Apoptosis; D002465:Cell Movement; D049109:Cell Proliferation; D018859:Hair Follicle / Q000166:cytology*; D019426:Integrases / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D062326:Re-Epithelialization; D055153:Stem Cell Niche; D013234:Stem Cells / Q000166:cytology*
chemical_list: C045073:Cre recombinase; D019426:Integrases
keywords: Bulge; Hair follicle; Skin; Wound healing