A single-cell transcriptomic landscape of mouse testicular aging

作者：Zhang, Wei; Xia, Siyu; Xiao, Wei; Song, Yali; Tang, Li; Cao, Min; Yang, Jing; Wang, Shuang; Li, Zhijie; Xu, Chengchao; Liu, Jianqiao^*; Zhao, Shanchao^*; Yang, Chuanbin^*; Wang, Jigang^*

来源：Journal of Advanced Research, 2023, 53: 219-234.

DOI：10.1016/j.jare.2022.12.007

• Aging
• Testis
• Single-cell RNA sequencing
• Senescence
• Inflammation

Introduction: Advanced paternal age of reproduction is an increasing trend, especially in developed coun-tries and areas. This trend results in elevated risks of adverse reproductive outcomes such as reduced fer-tility rates, increased pregnancy loss, and poor childhood health. Yet, a systematic profiling of aging -associated molecular and cellular alterations in testicular tissue is still missing. Objectives: We aimed to dissect aging-associated molecular characteristics in testes of mice. Methods: Single-cell transcriptomic sequencing and analysis were conducted in testes of young (2 months old) and old mice (24 months old). Immunofluorescences and immunochemistry were used to character-ize aging-associated phenotypes and verify single cell sequence results. Results: Here, we constructed the first single-cell transcriptomic atlases of testes of young and old mice. In-depth dissection of aging-dependent transcriptional alterations in specific cell types revealed multiple dysregulated biological processes such as increased 'senescence-associated secretory phenotype' and 'in-flammation', which were major aging-associated characteristics. Further analysis of aging-related differ-entially expressed genes uncovered a disrupted balance of undifferentiated and differentiated spermatogonia stem cells in spermatogonia, indicative of a potential role of spermatogonia stem cells in aging-associated subfertility. Importantly, for the first time, our results identified an increased subtype of aging-specific macrophages, which may contribute to a hostile proinflammatory microenvironment during testicular aging. Conclusion: Taken together, our findings depict the distinct single-cell transcriptional features of the aged mouse testes and provide enormous resources for a comprehensive understanding of the cell-type -specific molecular mechanisms underlying mouse testicular aging, which may shed light on developing novel potential diagnostic biomarkers and therapeutic targets for age-associated male subfertility.

• 单位
  南方医科大学; 1; 广东药学院; 广州医学院