Ubiquitin-Specific-Processing Protease 7 Regulates Female Germline Stem Cell Self-Renewal Through DNA Methylation.

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Tytuł:: Ubiquitin-Specific-Processing Protease 7 Regulates Female Germline Stem Cell Self-Renewal Through DNA Methylation.
Autorzy:: Zhao Y; Renji Hospital, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240, China.
Li X; Renji Hospital, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240, China.
Tian G; Renji Hospital, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240, China.
Zhao X; Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan, 750004, China.
Wong J; Shanghai Key Laboratory of Regulatory Biology, Fengxian District Central Hospital-ECNU Joint Center of Translational Medicine, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China.
Shen Y; Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan, 750004, China.
Wu J; Renji Hospital, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240, China. .; Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan, 750004, China. .
Źródło:: Stem cell reviews and reports [Stem Cell Rev Rep] 2021 Jun; Vol. 17 (3), pp. 938-951. Date of Electronic Publication: 2020 Nov 05.
Typ publikacji:: Journal Article; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Publication: 2011- : [New York, NY] : Springer Science+Business Media
Original Publication: [Totowa, N.J.] : Humana Press, [2009]-
MeSH Terms:: DNA Methylation*/genetics
Oogonial Stem Cells*
Female ; Humans ; Ubiquitin-Specific Peptidase 7 ; Ubiquitins
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Contributed Indexing:: Keywords: DNA methylation; Differentiation; FGSCs; Histone modification; Self-renewal; Usp7
Substance Nomenclature:: 0 (Ubiquitins)
EC 3.4.19.12 (Ubiquitin-Specific Peptidase 7)
Entry Date(s):: Date Created: 20201105 Date Completed: 20220307 Latest Revision: 20220307
Update Code:: 20231215
PubMed Central ID:: PMC8166723
DOI:: 10.1007/s12015-020-10076-9
PMID:: 33151468
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Ubiquitin-specific-processing protease 7 (Usp7) is a key deubiquitinase controlling epigenetic modification and regulating the self-renewal, proliferation, and differentiation of stem cells. However, the functions and mechanisms of action of Usp7 on female germline stem cells (FGSCs) are unknown. Here, we demonstrated that Usp7 regulated FGSC self-renewal via DNA methylation. The results of Cell Counting Kit-8 and 5-ethynyl-20-deoxyuridine assays showed that the viability and proliferation of FGSCs were negatively regulated by Usp7. Moreover, Usp7 downregulated the expression of self-renewal genes, such as Oct4, Etv5, Foxo1, and Akt, but upregulated the expression of differentiation-related genes including Stra8 and Sycp3. Mechanistically, RNA-seq results showed that Usp7 negatively regulated FGSC self-renewal but positively modulated differentiation in FGSCs. Meanwhile, both overexpression and knockdown of Usp7 resulted in significant changes in DNA methylation and histone modification in FGSCs. Additionally, RNA-seq and MeDIP-seq analyses showed that Usp7 regulates the self-renewal and differentiation of FGSCs mainly through DNA methylation rather than histone modification, which was also confirmed by a rescue assay. Our study not only offers a novel method to research FGSC self-renewal and differentiation in view of epigenetic modifications, but also provides a deep understanding of FGSC development. Graphical Abstract.

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