title: Atypical Protein Kinase C Isoform, aPKCλ, Is Essential for Maintaining Hair Follicle Stem Cell Quiescence.
abstract: The atypical protein kinase C (aPKC)-partition-defective (PAR) complex regulates the formation of tight junctions and apico-basal epithelial polarity. To examine the role of this complex in the epidermis, we generated mutant mice harboring epidermal-specific deletion of aPKCλ (conditional knock-out (cKO)), a major component of the aPKC-PAR complex. The mutant mice exhibited abnormal hair follicle (HF) cycling, progressive losses of pelage hairs and vibrissae, and altered differentiation into the epidermis and sebaceous gland. We found that in the aPKCλ cKO mice HF stem cell (HFSC) quiescence was lost, as revealed by the decreased expression level of quiescence-inducing factors (Fgf18 and Bmp6) produced in Keratin 6-positive bulge stem cells. The loss of quiescence dysregulated the HFSC marker expression and led to the increase in Lrig1-positive cells, inducing hyperplasia of the interfollicular epidermis and sebaceous glands, and drove an increase in Lef1-positive matrix cells, causing a prolonged anagen-like phase. Persistent bulge stem cell activation led to a gradual depletion of CD34- and α6 integrin-positive HFSC reservoirs. These results suggest that aPKCλ regulates signaling pathways implicated in HFSC quiescence.
authors.affiliation: Department of Dermatology, Nippon Medical School, Tokyo, Japan. Electronic address: ohnos@med.yokohama-cu.ac.jp.
authors.forename: Shin-Ichi
authors.initials: SI
authors.lastname: Osada
authors.affiliation: Department of Dermatology, Nippon Medical School, Tokyo, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Minematsu
authors.affiliation: Department of Dermatology, Nippon Medical School, Tokyo, Japan.
authors.forename: Fumino
authors.initials: F
authors.lastname: Oda
authors.affiliation: Department of Molecular Biology, Yokohama City University Graduate School of Medical Science, Yokohama, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Akimoto
authors.affiliation: Department of Dermatology, Nippon Medical School, Tokyo, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Kawana
authors.affiliation: Department of Molecular Biology, Yokohama City University Graduate School of Medical Science, Yokohama, Japan. Electronic address: ohnos@med.yokohama-cu.ac.jp.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ohno
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D017353:Gene Deletion; D005819:Genetic Markers; D018859:Hair Follicle / Q000166:cytology* / Q000473:pathology; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D051379:Mice; D018345:Mice, Knockout; D020033:Protein Isoforms / Q000378:metabolism; D011493:Protein Kinase C / Q000235:genetics* / Q000378:metabolism*; D011897:Random Allocation; D060888:Real-Time Polymerase Chain Reaction; D012016:Reference Values; D015398:Signal Transduction / Q000235:genetics; D013234:Stem Cells / Q000378:metabolism*
chemical_list: D005819:Genetic Markers; D020033:Protein Isoforms; C115015:PKC-3 protein; D011493:Protein Kinase C; D001973:Bromodeoxyuridine