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

Zhao, Yue; Li, Xiaoyong; Tian, Geng; Zhao, Xinyan; Wong, Jiemin; Shen, Yue; Wu, Ji

doi:10.1007/s12015-020-10076-9

Cited by 3 publications

(1 citation statement)

References 52 publications

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“…Our previous study found that DNA methylation is involved in the unipotency of FGSCs and maintains their sexual identity 12 . Zhao et al showed that Usp7 regulates the self-renewal and differentiation of FGSCs through DNA methylation 13 . In addition, long noncoding RNA 14 , 15 , Circular RNA 16 , and m6A modification 17 have been reported to participate in the epigenetic regulation of FGSCs development.…”

Section: Introductionmentioning

confidence: 99%

Stella Regulates the Development of Female Germline Stem Cells by Modulating Chromatin Structure and DNA Methylation

Hou¹,

Zhao²,

Tian³

et al. 2022

Int. J. Biol. Sci.

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Female germline stem cells (FGSCs) have the ability to self-renew and differentiate into oocytes. Stella , encoded by a maternal effect gene, plays an important role in oogenesis and early embryonic development. However, its function in FGSCs remains unclear. In this study, we showed that CRISPR/Cas9-mediated knockout of Stella promoted FGSC proliferation and reduced the level of genome-wide DNA methylation of FGSCs. Conversely, Stella overexpression led to the opposite results, and enhanced FGSC differentiation. We also performed an integrative analysis of chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq), high-throughput genome-wide chromosome conformation capture (Hi-C), and use of our published epigenetic data. Results indicated that the binding sites of STELLA and active histones H3K4me3 and H3K27ac were enriched near the TAD boundaries. Hi-C analysis showed that Stella overexpression attenuated the interaction within TADs, and interestingly enhanced the TAD boundary strength in STELLA-associated regions. Taking these findings together, our study not only reveals the role of Stella in regulating DNA methylation and chromatin structure, but also provides a better understanding of FGSC development.

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Section: Introductionmentioning

confidence: 99%

Stella Regulates the Development of Female Germline Stem Cells by Modulating Chromatin Structure and DNA Methylation

Hou¹,

Zhao²,

Tian³

et al. 2022

Int. J. Biol. Sci.

Self Cite

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Serum- and Feeder-Free Culture of Juvenile Monkey Female Germline Stem Cells and Testosterone Regulation of their Self-Renewal

Yao

et al. 2021

Stem Cell Rev and Rep

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Deubiquitylase ubiquitin-specific protease 7 plays a crucial role in the lineage differentiation of preimplantation blastocysts

Yu,

Zhao,

Tang

et al. 2024

Biology of Reproduction

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Preimplantation embryos undergo a series of important biological events, including epigenetic reprogramming and lineage differentiation, and the key genes and specific mechanisms that regulate these events are critical to reproductive success. USP7 is a deubiquitinase involved in the regulation of a variety of cellular functions, yet its precise function and mechanism in preimplantation embryonic development remain unknown. Our results showed that RNAi-mediated silencing of USP7 in mouse embryos or treatment with P5091, a small molecule inhibitor of USP7, significantly reduced blastocyst rate and blastocyst quality, and decreased total and TE cell numbers per blastocyst, as well as destroying normal lineage differentiation. The results of single-cell RNA-seq, RT-qPCR, western blot, and immunofluorescence staining indicated that interference with USP7 caused failure of the morula-to-blastocyst transition and was accompanied by abnormal expression of key genes (Cdx2, Oct4, Nanog, Sox2) for lineage differentiation, decreased transcript levels, increased global DNA methylation, elevated repressive histone marks (H3K27me3), and decreased active histone marks (H3K4me3 and H3K27ac). Notably, USP7 may regulate the transition from the morula to blastocyst by stabilizing the target protein YAP through the ubiquitin-proteasome pathway. In conclusion, our results suggest that USP7 may play a crucial role in preimplantation embryonic development by regulating lineage differentiation and key epigenetic modifications.

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

Cited by 3 publications

References 52 publications

Stella Regulates the Development of Female Germline Stem Cells by Modulating Chromatin Structure and DNA Methylation

Stella Regulates the Development of Female Germline Stem Cells by Modulating Chromatin Structure and DNA Methylation

Serum- and Feeder-Free Culture of Juvenile Monkey Female Germline Stem Cells and Testosterone Regulation of their Self-Renewal

Deubiquitylase ubiquitin-specific protease 7 plays a crucial role in the lineage differentiation of preimplantation blastocysts

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