Shakeri Abroudi Ali, Azizi Hossein, Djamali Melika, Qorbanee Ali, Skutella Thomas
Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran 1936893813, Iran.
Faculty of Biotechnology, Amol University of Special Modern Technologies, Amol 4615664616, Iran.
Biology (Basel). 2025 Apr 8;14(4):387. doi: 10.3390/biology14040387.
Histone modifications play a critical role in regulating gene expression and maintaining the functionality of spermatogonial stem cells (SSCs), which are essential for male fertility and spermatogenesis. In this study, we integrated microarray and single-cell RNA-sequencing (scRNA-seq) data to identify key histone modification gene changes associated with SSC function and aging. Through differential expression analysis, we identified 2509 differentially expressed genes (DEGs) in SSCs compared to fibroblasts. Among these, genes involved in histone modification, such as KDM5B, SCML2, SIN3A, and ASXL3, were highlighted for their significant roles in chromatin remodeling and gene regulation. Protein-protein interaction (PPI) networks and gene ontology (GO) enrichment analysis revealed critical biological processes such as chromatin organization, histone demethylation, and chromosome structure maintenance. Weighted gene co-expression network analysis (WGCNA) further revealed three key modules of co-expressed genes related to spermatogonial aging. Additionally, ligand-receptor interaction scoring based on tumor microenvironment analysis suggested potential signaling pathways that could influence the stemness and differentiation of SSCs. Our findings provide new insights into the molecular mechanisms underlying SSC aging, highlighting histone modification genes as potential therapeutic targets for preserving male fertility and improving SSC-culturing techniques. This study advances our understanding of histone modification in SSC biology and will serve as a valuable resource for future investigations into male fertility preservation.
组蛋白修饰在调节基因表达和维持精原干细胞（SSCs）的功能中起着关键作用，而精原干细胞对于男性生育能力和精子发生至关重要。在本研究中，我们整合了微阵列和单细胞RNA测序（scRNA-seq）数据，以确定与精原干细胞功能和衰老相关的关键组蛋白修饰基因变化。通过差异表达分析，我们确定了与成纤维细胞相比，精原干细胞中有2509个差异表达基因（DEGs）。其中，参与组蛋白修饰的基因，如KDM5B、SCML2、SIN3A和ASXL3，因其在染色质重塑和基因调控中的重要作用而受到关注。蛋白质-蛋白质相互作用（PPI）网络和基因本体（GO）富集分析揭示了染色质组织、组蛋白去甲基化和染色体结构维持等关键生物学过程。加权基因共表达网络分析（WGCNA）进一步揭示了与精原细胞衰老相关的三个关键共表达基因模块。此外，基于肿瘤微环境分析的配体-受体相互作用评分表明了可能影响精原干细胞干性和分化的潜在信号通路。我们的研究结果为精原干细胞衰老的分子机制提供了新的见解，突出了组蛋白修饰基因作为保护男性生育能力和改进精原干细胞培养技术的潜在治疗靶点。这项研究推进了我们对精原干细胞生物学中组蛋白修饰的理解，并将成为未来男性生育力保护研究的宝贵资源。
