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Abstract：
Advancing healthcare for elderly men requires a deeper understanding of testicular aging processes. In this study, we conducted transcriptomic profiling of 43,323 testicular single cells from young and old mice, shedding light on 1032 telocytes-an underexplored testicular cell type in previous research. Our study unveiled 916 age-related differentially expressed genes (age-DEGs), with telocytes emerging as the cell type harboring the highest count of age-DEGs. Of particular interest, four genes (Klk1b21, Klk1b22, Klk1b24, Klk1b27) from the Kallikrein family, specifically expressed in Leydig cells, displayed down-regulation in aged testes. Moreover, cell-type-level splicing analyses unveiled 1838 age-related alternative splicing (AS) events. While we confirmed the presence of more age-DEGs in somatic cells compared to germ cells, unexpectedly, more age-related AS events were identified in germ cells. Further experimental validation highlighted 4930555F03Rik, a non-coding RNA gene exhibiting significant age-related AS changes. Our study represents the first age-related single-cell transcriptomic investigation of testicular telocytes and Kallikrein genes in Leydig cells, as well as the first delineation of cell-type-level AS dynamics during testicular aging in mice.
摘要：
推进老年男性的医疗保健需要对睾丸衰老过程有更深入的了解。在这项研究中,我们对来自年轻和老年小鼠的43,323个睾丸单细胞进行了转录组学分析，在1032个端粒细胞上发光-以前研究中发育不足的睾丸细胞类型。我们的研究揭示了916个与年龄相关的差异表达基因（年龄-DEG），端粒细胞作为年龄DEG计数最高的细胞类型出现。特别感兴趣的是，来自Kallikrein家族的四个基因（Klk1b21，Klk1b22，Klk1b24，Klk1b27），在Leydig细胞中特异性表达，在老化的睾丸中显示下调。此外，细胞类型水平剪接分析揭示了1838个年龄相关的选择性剪接（AS）事件。虽然我们证实了与生殖细胞相比，体细胞中存在更多的年龄-DEG，出乎意料的是,在生殖细胞中发现了更多与年龄相关的AS事件.进一步的实验验证突出显示4930555F03Rik，非编码RNA基因表现出显著的与年龄相关的AS变化。我们的研究代表了睾丸端细胞和激肽释放酶基因在Leydig细胞中的第一个年龄相关的单细胞转录组学研究。以及小鼠睾丸衰老过程中细胞类型水平AS动力学的首次描述。
