Essential Roles of Cyclin Y-Like 1 and Cyclin Y in Dividing Wnt-Responsive Mammary Stem/Progenitor Cells

被引：32

作者：

Zeng, Liyong ^{[1
]}

Cai, Cheguo ^{[1
]}

Li, Shan ^{[2
]}

Wang, Wenjuan ^{[2
]}

Li, Yaping ^{[1
,3
]}

Chen, Jiangye ^{[2
]}

Zhu, Xueliang ^{[1
]}

Zeng, Yi Arial ^{[1
]}

机构：

[1] Chinese Acad Sci, Shanghai Inst Biol Sci, CAS Ctr Excellence Mol Cell Sci, State Key Lab Cell Biol,Inst Biochem & Cell Biol, Shanghai, Peoples R China

[2] Chinese Acad Sci, Shanghai Inst Biol Sci, State Key Lab Mol Biol, Inst Biochem & Cell Biol, Shanghai, Peoples R China

[3] ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China

来源：

PLOS GENETICS | 2016年 / 12卷 / 05期

基金：

中国国家自然科学基金;

关键词：

HEMATOPOIETIC STEM-CELLS; SELF-RENEWAL; GLAND DEVELOPMENT; RECEPTOR ACTIVATION; SMALL-INTESTINE; BETA-CATENIN; G1; PHASE; IN-VITRO; MOUSE; DIFFERENTIATION;

D O I：

10.1371/journal.pgen.1006055

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Cyclin Y family can enhance Wnt/beta-catenin signaling in mitosis. Their physiological roles in mammalian development are yet unknown. Here we show that Cyclin Y-like 1 (Ccnyl1) and Cyclin Y (Ccny) have overlapping function and are crucial for mouse embryonic development and mammary stem/progenitor cell functions. Double knockout of Ccnys results in embryonic lethality at E16.5. In pubertal development, mammary terminal end buds robustly express Ccnyl1. Depletion of Ccnys leads to reduction of Lrp6 phosphorylation, hampering beta-catenin activities and abolishing mammary stem/progenitor cell expansion in vitro. In lineage tracing experiments, Ccnys-deficient mammary cells lose their competitiveness and cease to contribute to mammary development. In transplantation assays, Ccnys-deficient mammary cells fail to reconstitute, whereas constitutively active beta-catenin restores their regeneration abilities. Together, our results demonstrate the physiological significance of Ccnys-mediated mitotic Wnt signaling in embryonic development and mammary stem/progenitor cells, and reveal insights in the molecular mechanisms orchestrating cell cycle progression and maintenance of stem cell properties.

引用

页数：21

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