Lgr4 Regulates Mammary Gland Development and Stem Cell Activity Through the Pluripotency Transcription Factor Sox2

被引：73
|
作者：
Wang, Ying [1 ,2 ,3 ]
Dong, Jie [4 ]
Li, Dali [1 ,2 ]
Lai, Li [1 ,2 ,3 ]
Siwko, Stefan [3 ]
Li, Yi [4 ]
Liu, Mingyao [1 ,2 ,3 ]
机构：
[1] E China Normal Univ, Inst Biomed Sci, Shanghai Key Lab Regulatory Biol, Shanghai 200062, Peoples R China
[2] E China Normal Univ, Sch Life Sci, Shanghai 200062, Peoples R China
[3] Texas A&M Univ Hlth Sci Ctr, Inst Biosci & Technol, Ctr Canc & Stem Cell Biol, Houston, TX USA
[4] Baylor Coll Med, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA
来源：
STEM CELLS | 2013年 / 31卷 / 09期
基金：
中国国家自然科学基金;
关键词：
Lgr4; Gpr48; Mammary stem cell; Sox2; Wnt signaling; COUPLED RECEPTOR 48; MALE REPRODUCTIVE-TRACT; SELF-RENEWAL; WNT/BETA-CATENIN; HAIR FOLLICLE; IN-VITRO; BRANCHING MORPHOGENESIS; STEM/PROGENITOR CELLS; POSTNATAL-DEVELOPMENT; DOWN-REGULATION;
D O I：
10.1002/stem.1438
中图分类号：
Q813 [细胞工程];
学科分类号：
摘要：
The key signaling networks regulating mammary stem cells are poorly defined. The leucine-rich repeat containing G protein-coupled receptor (Lgr) family has been implicated in intestinal, gastric, and epidermal stem cell functions. We investigated whether Lgr4 functions in mammary gland development and mammary stem cells. We found that Lgr4(-/-) mice had delayed ductal development, fewer terminal end buds, and decreased side-branching. Crucially, the mammary stem cell repopulation capacity was severely impaired. Mammospheres from Lgr4(-/-) mice showed decreased Wnt signaling. Wnt3a treatment prevented the adverse effects of Lgr4 loss on organoid formation. Chromatin immunoprecipitation analysis indicated that Sox2 expression was controlled by the Lgr4/Wnt/-catenin/Lef1 pathway. Importantly, Sox2 overexpression restored the in vivo mammary regeneration potential of Lgr4(-/-) mammary stem cells. Therefore, Lgr4 activates Sox2 to regulate mammary development and stem cell functions via Wnt/-catenin/Lef1. Stem Cells2013;31:1921-1931
引用
收藏
页码：1921 / 1931
页数：11
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