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MAGEB2-Mediated Degradation of EGR1 Regulates the Proliferation and Apoptosis of Human Spermatogonial Stem Cell Lines
Xueheng Zhao1,2, Zenghui Huang1,2, Yongzhe Chen3
1Institute of Reproduction and Stem Cell Engineering, School of Basic Medicine Science, Central South University, Changsha, Hunan 410000, China.
Abstract:
Spermatogonial stem cells are committed to initiating and maintaining male spermatogenesis, which is the foundation of male fertility. Understanding the mechanisms underlying SSC fate decisions is critical for controlling spermatogenesis and male fertility. However, the key molecules and mechanisms responsible for regulating human SSC development are not clearly understood. Here, we analyzed normal human testis single-cell sequencing data from the GEO dataset (GSE149512 and GSE112013). Melanoma antigen gene B2 (MAGEB2) was found to be predominantly expressed in human SSCs and further validated by immunohistology. Overexpression of MAGEB2 in SSC lines severely weakened cell proliferation and promoted apoptosis. Further, using protein interaction prediction, molecular docking, and immunoprecipitation, we found that MAGEB2 interacted with early growth response protein 1 (EGR1) in SSC lines. Reexpression of EGR1 in MAGEB2 overexpression cells partially rescued decreased cell proliferation. Furthermore, MAGEB2 was shown to be downregulated in specific NOA patients, implying that abnormal expression of MAGEB2 may impair spermatogenesis and male fertility. Our results offer new insights into the functional and regulatory mechanisms in MAGEB2-mediated human SSC line proliferation and apoptosis.
Insights
Melanoma antigen gene B2 (MAGEB2) is crucial for human spermatogonial stem cell (SSC) proliferation and survival. Its dysregulation impairs male fertility, highlighting MAGEB2
Area of Science:
- Reproductive Biology
- Cell Biology
- Molecular Biology
Background:
- Spermatogonial stem cells (SSCs) are vital for male fertility, initiating and maintaining spermatogenesis.
- Understanding human SSC regulation is crucial but remains incomplete.
- Key molecular mechanisms controlling human SSC fate are largely unknown.
Purpose of the Study:
- To investigate the role of Melanoma Antigen Gene B2 (MAGEB2) in human SSCs.
- To identify molecular interactions regulating SSC proliferation and apoptosis.
- To explore MAGEB2's potential link to male infertility.
Main Methods:
- Analysis of human testis single-cell sequencing data (GEO datasets GSE149512, GSE112013).
- Immunohistology to validate MAGEB2 expression.
- In vitro experiments with SSC lines to assess MAGEB2 overexpression effects.
- Protein interaction prediction, molecular docking, and immunoprecipitation to identify MAGEB2 interacting partners.
- Analysis of MAGEB2 expression in Non-Obstructive Azoospermia (NOA) patients.
Main Results:
- MAGEB2 is predominantly expressed in human SSCs.
- MAGEB2 overexpression in SSC lines reduced proliferation and increased apoptosis.
- MAGEB2 interacts with Early Growth Response Protein 1 (EGR1) in SSCs.
- Re-expression of EGR1 partially rescued MAGEB2-induced proliferation defects.
- MAGEB2 was downregulated in some NOA patients.
Conclusions:
- MAGEB2 plays a significant role in regulating human SSC proliferation and apoptosis.
- The MAGEB2-EGR1 interaction is important for SSC proliferation.
- MAGEB2 downregulation may contribute to impaired spermatogenesis and male infertility.
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