title: Essential Roles of Cyclin Y-Like 1 and Cyclin Y in Dividing Wnt-Responsive Mammary Stem/Progenitor Cells.
abstract: Cyclin Y family can enhance Wnt/β-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 β-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 β-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.
authors.affiliation: State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Liyong
authors.initials: L
authors.lastname: Zeng
authors.affiliation: State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Cheguo
authors.initials: C
authors.lastname: Cai
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Li
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.|School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Jiangye
authors.initials: J
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Xueliang
authors.initials: X
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yi Arial
authors.initials: YA
authors.lastname: Zeng
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D016213:Cyclins / Q000235:genetics*; D047108:Embryonic Development / Q000235:genetics*; D005260:Female; D060488:Low Density Lipoprotein Receptor-Related Protein-6 / Q000235:genetics; D008321:Mammary Glands, Animal / Q000254:growth & development / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D011247:Pregnancy; D012038:Regeneration / Q000235:genetics; D060449:Wnt Signaling Pathway / Q000235:genetics; D051176:beta Catenin / Q000235:genetics
chemical_list: C000606102:Ccnyl1 protein, mouse; D016213:Cyclins; D060488:Low Density Lipoprotein Receptor-Related Protein-6; C555476:Lrp6 protein, mouse; D051176:beta Catenin; C000606718:cyclin Y, mouse