CARF promotes spermatogonial self-renewal and proliferation through Wnt signaling pathway
2020-12-17
发表期刊CELL DISCOVERY (IF:13.0[JCR-2023],14.8[5-Year])
卷号6期号:1
发表状态已发表
DOI10.1038/s41421-020-00212-7
摘要Collaborator of ARF (CARF) regulates cell proliferative fate through both p53-dependent and -independent mechanisms. Recently, we reported a new function of CARF as a positive regulator of Wnt signaling. Despite these findings, the physiological function of CARF has not been well studied. Here, we generated CARF knockout mice and found that male CARF(-/-) mice exhibited significantly impaired fertility and Sertoli-cell-only (SCO) syndrome phenotypes. Further studies revealed that loss of CARF in Sertoli cells led to decreased GDNF expression, which hindered spermatogonial stem cells (SSCs) self-renewal. Meanwhile, CARF loss in undifferentiated spermatogonia impaired their proliferation. These two mechanisms together led to SCO syndrome phenotypes, which could be functionally rescued by pharmacological or genetic reactivation of Wnt signaling. Finally, we identified CARF(S351F) as a potential pathogenic mutation in an SCO patient. Overall, our findings reveal important roles of CARF in spermatogonial self-renewal and proliferation through the Wnt signaling pathway.
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收录类别SCI ; SCIE
语种英语
资助项目National Natural Science Foundation of China[31530094] ; Ministry of Science and Technology of China[2017YF0503600] ; CAS Strategic Priority Research Program[XDB19030000]
WOS研究方向Cell Biology
WOS类目Cell Biology
WOS记录号WOS:000591262300001
出版者SPRINGERNATURE
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文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/124608
专题生命科学与技术学院_博士生
生命科学与技术学院_特聘教授组_李林组
通讯作者Li, Lin
作者单位
1.Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, State Key Lab Mol Biol,CAS Ctr Excellence Mol Cel, Shanghai 200031, Peoples R China
2.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
3.Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Anhui, Peoples R China
4.Yale Sch Med, Vasc Biol & Therapeut Program, New Haven, CT 06520 USA
5.Yale Sch Med, Dept Pharmacol, New Haven, CT 06520 USA
6.Univ Chinese Acad Sci, Sch Life Sci, Hangzhou Inst Adv Study, Hangzhou 310024, Zhejiang, Peoples R China
第一作者单位生命科学与技术学院
通讯作者单位生命科学与技术学院
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GB/T 7714
Cui, Wenhao,He, Xiaoli,Zhai, Xiaohong,et al. CARF promotes spermatogonial self-renewal and proliferation through Wnt signaling pathway[J]. CELL DISCOVERY,2020,6(1).
APA Cui, Wenhao.,He, Xiaoli.,Zhai, Xiaohong.,Zhang, Huan.,Zhang, Yuanwei.,...&Li, Lin.(2020).CARF promotes spermatogonial self-renewal and proliferation through Wnt signaling pathway.CELL DISCOVERY,6(1).
MLA Cui, Wenhao,et al."CARF promotes spermatogonial self-renewal and proliferation through Wnt signaling pathway".CELL DISCOVERY 6.1(2020).
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