title: Activation of β-Catenin Signaling in CD133-Positive Dermal Papilla Cells Drives Postnatal Hair Growth.
abstract: The hair follicle dermal papilla (DP) contains a unique prominin-1/CD133-positive (CD133+) cell subpopulation, which has been shown to possess hair follicle-inducing capability. By assaying for endogenous CD133 expression and performing lineage tracing using CD133-CreERT2; ZsGreen1 reporter mice, we find that CD133 is expressed in a subpopulation of DP cells during the growth phase of the murine hair cycle (anagen), but is absent at anagen onset. However, how CD133+ DP cells interact with keratinocytes to induce hair regenerative growth remains unclear. Wnt/β-catenin has long been recognized as a major signaling pathway required for hair follicle morphogenesis, development, and regeneration. Nuclear Wnt/β-catenin activity is observed in the DP during the hair growth phase. Here we show that induced expression of a stabilized form of β-catenin in CD133+ DP cells significantly accelerates spontaneous and depilation-induced hair growth. However, hair follicle regression is not affected in these mutants. Further analysis indicates that CD133+ DP-expressed β-catenin increases proliferation and differentiation of epithelial matrix keratinocytes. Upregulated Wnt/β-catenin activity in CD133+ DP cells also increases the number of proliferating DP cells in each anagen follicle. Our data demonstrate that β-catenin signaling potentiates the capability of CD133+ DP cells to promote postnatal hair growth.
authors.affiliation: Division of Pharmaceutical Sciences, College of Pharmacy, University of Cincinnati, Cincinnati, Ohio 45267, United States of America.
authors.forename: Linli
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104, United States of America.
authors.forename: Mingang
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Cancer Biology, Vontz Center for Molecular Studies, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, United States of America.
authors.forename: Yongguang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Division of Pharmaceutical Sciences, College of Pharmacy, University of Cincinnati, Cincinnati, Ohio 45267, United States of America.
authors.forename: Kun
authors.initials: K
authors.lastname: Yang
authors.affiliation: Division of Pharmaceutical Sciences, College of Pharmacy, University of Cincinnati, Cincinnati, Ohio 45267, United States of America.
authors.forename: Randall R
authors.initials: RR
authors.lastname: Wickett
authors.affiliation: Burnett School of Biomedical Sciences, University of Central Florida, Orlando, Florida 32826, United States of America.
authors.forename: Thomas
authors.initials: T
authors.lastname: Andl
authors.affiliation: Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104, United States of America.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Millar
authors.affiliation: Division of Pharmaceutical Sciences, College of Pharmacy, University of Cincinnati, Cincinnati, Ohio 45267, United States of America.
authors.forename: Yuhang
authors.identifier: http://orcid.org/0000-0002-9738-5343
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000071916:AC133 Antigen / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D018859:Hair Follicle / Q000378:metabolism; D051379:Mice; D015398:Signal Transduction; D012867:Skin / Q000166:cytology / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D000071916:AC133 Antigen; D051176:beta Catenin