Study on DNA damage gene in spermatogonial stem cells from idiopathic non-obstructive azoospermia(NOA) : an bioinformatics investigation based on scRNA-seq data.
Yi Wang, Yiming Weng, Yanqiu Wang, Jun Xiang, Wei Le
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引用次数: 0
Abstract
Introduction: DNA damage may affect homeostasis on spermatogonial stem cells(SSCs), while the details relationship with male infertility still remains unclear. Therefore, it is important that further research into the mechanisms related to DNA damage and genomic stability on spermatogonial stem cells.
Methods: scRNA-seq datasets from Idiopathic non-obstructive azoospermia (NOA) and normal testes were collected and testicular cells were further annotated via UMAP. Based annotation on the sequencing data, WGCNA analysis on the deferentially expressed genes was conducted , LASSO regression and the MNC calculation algorithm in Cytoscape were carried out to find genes associated with DNA damage repair.
Results: It was found that SSCs were mainly concentrated in normal samples, and the differences in subcluster pathways reflected the heterogeneity of NOA. While the characteristics of the interaction between Leydig cells and other cells were clarified, and the importance of the PTN signaling pathway in SSCs development was discovered, which participates in SSCs development through SDC2. Combining the marker genes of SSCs and DNA damage-related genes in single-cell analysis, a PPI network was constructed. Through LASSO regression and the MNC calculation algorithm in Cytoscape, ATRX, DOT1L, and RUVBL2 were finally identified as key diagnostic genes.
Conclusion: Our results revealed predictable mechanisms of testicular micro-environment and DNA damage in the regulation of human SSCs and propose potential therapeutic targets for male infertility. Subsequently, further research to confirm the predicted potential mechanisms, pathways, and therapeutic targets should be conducted.
期刊介绍:
During the last decades, ''Cytogenetic and Genome Research'' has been the leading forum for original reports and reviews in human and animal cytogenetics, including molecular, clinical and comparative cytogenetics. In recent years, most of its papers have centered on genome research, including gene cloning and sequencing, gene mapping, gene regulation and expression, cancer genetics, comparative genetics, gene linkage and related areas. The journal also publishes key papers on chromosome aberrations in somatic, meiotic and malignant cells. Its scope has expanded to include studies on invertebrate and plant cytogenetics and genomics. Also featured are the vast majority of the reports of the International Workshops on Human Chromosome Mapping, the reports of international human and animal chromosome nomenclature committees, and proceedings of the American and European cytogenetic conferences and other events. In addition to regular issues, the journal has been publishing since 2002 a series of topical issues on a broad variety of themes from cytogenetic and genome research.