Distinct Functions for Wnt/β-Catenin in Hair Follicle Stem Cell Proliferation and Survival and Interfollicular Epidermal Homeostasis

被引:274
作者
Choi, Yeon Sook [1 ]
Zhang, Yuhang [1 ,2 ]
Xu, Mingang [1 ]
Yang, Yongguang [2 ]
Ito, Mayumi [1 ]
Peng, Tien [3 ]
Cui, Zheng [3 ]
Nagy, Andras [4 ]
Hadjantonakis, Anna-Katerina [5 ]
Lang, Richard A. [6 ,7 ]
Cotsarelis, George [1 ]
Andl, Thomas [1 ]
Morrisey, Edward E. [3 ]
Millar, Sarah E. [1 ,8 ]
机构
[1] Univ Penn, Perelman Sch Med, Dept Dermatol, Philadelphia, PA 19104 USA
[2] Univ Cincinnati, Coll Pharm, Div Pharmaceut Sci, Cincinnati, OH 45267 USA
[3] Univ Penn, Perelman Sch Med, Dept Med, Div Cardiol, Philadelphia, PA 19104 USA
[4] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada
[5] Sloan Kettering Inst, Dev Biol Program, New York, NY 10065 USA
[6] Cincinnati Childrens Hosp Med Ctr, Div Pediat Ophthalmol, Cincinnati, OH 45229 USA
[7] Cincinnati Childrens Hosp Med Ctr, Div Dev Biol, Cincinnati, OH 45229 USA
[8] Univ Penn, Perelman Sch Med, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA
关键词
BETA-CATENIN; GENE-EXPRESSION; MORPHOGENESIS; ACTIVATION; BULGE; DIFFERENTIATION; KERATINOCYTES; MAINTENANCE; INITIATION; PROTEINS;
D O I
10.1016/j.stem.2013.10.003
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Wnt/beta-catenin signaling is a central regulator of adult stem cells. Variable sensitivity of Wnt reporter transgenes, beta-catenin's dual roles in adhesion and signaling, and hair follicle degradation and inflammation resulting from broad deletion of epithelial beta-catenin have precluded clear understanding of Wnt/beta-catenin's functions in adult skin stem cells. By inducibly deleting beta-catenin globally in skin epithelia, only in hair follicle stem cells, or only in interfollicular epidermis and comparing the phenotypes with those caused by ectopic expression of the Wnt/beta-catenin inhibitor Dkk1, we show that this pathway is necessary for hair follicle stem cell proliferation. However, beta-catenin is not required within hair follicle stem cells for their maintenance, and follicles resume proliferating after ectopic Dkk1 has been removed, indicating persistence of functional progenitors. We further unexpectedly discovered a broader role for Wnt/beta-catenin signaling in contributing to progenitor cell proliferation in nonhairy epithelia and interfollicular epidermis under homeostatic, but not inflammatory, conditions.
引用
收藏
页码:720 / 733
页数:14
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