Chen Xia, Qi Yujuan, Huang Qiuru, Sun Chi, Zheng Yanli, Ji Li, Shi Yi, Cheng Xinmeng, Li Zhenbei, Zheng Sen, Cao Yijuan, Gu Zhifeng, Yu Jun
Department of Obstetrics and Gynecology, Nantong First People's Hospital, Affiliated Hospital 2 of Nantong University; Medical School of Nantong University, Nantong University, Nantong, Jiangsu, China.
Clinical Center of Reproductive Medicine, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, Xuzhou, China.
Aging Cell. 2024 Mar;23(3):e14057. doi: 10.1111/acel.14057. Epub 2023 Dec 3.
Aging is a complex biological process leading to impaired functions, with a variety of hallmarks. In the testis of Drosophila, the terminal epithelium region is involved in spermatid release and maturation, while its functional diversity and regulatory mechanism remain poorly understood. In this study, we performed single-cell RNA-sequencing analysis (scRNA-seq) to characterize the transcriptomes of terminal epithelium in Drosophila testes at 2-, 10 and 40-Days. Terminal epithelium populations were defined with Metallothionein A (MtnA) and subdivided into six novel sub-cell clusters (EP0-EP5), and a series of marker genes were identified based on their expressions. The data revealed the functional characteristics of terminal epithelium populations, such as tight junction, focal adhesion, bacterial invasion, oxidative stress, mitochondrial function, proteasome, apoptosis and metabolism. Interestingly, we also found that disrupting genes for several relevant pathways in terminal epithelium led to male fertility disorders. Moreover, we also discovered a series of age-biased genes and pseudotime trajectory mediated state-biased genes during terminal epithelium aging. Differentially expressed genes during terminal epithelium aging were mainly participated in the regulation of several common signatures, e.g. mitochondria-related events, protein synthesis and degradation, and metabolic processes. We further explored the Drosophila divergence and selection in the functional constraints of age-biased genes during aging, revealing that age-biased genes in epithelial cells of 2 Days group evolved rapidly and were endowed with greater evolutionary advantages. scRNA-seq analysis revealed the diversity of testicular terminal epithelium populations, providing a gene target resource for further systematic research of their functions during aging.
衰老 是一个导致功能受损的复杂生物学过程，具有多种特征。在果蝇的睾丸中，终末上皮区域参与精子释放和成熟，但其功能多样性和调控机制仍知之甚少。在本研究中，我们进行了单细胞RNA测序分析（scRNA-seq），以表征果蝇睾丸在2天、10天和40天时终末上皮的转录组。利用金属硫蛋白A（MtnA）定义终末上皮群体，并将其细分为六个新的亚细胞簇（EP0-EP5），并根据其表达鉴定了一系列标记基因。数据揭示了终末上皮群体的功能特征，如紧密连接、粘着斑、细菌入侵、氧化应激、线粒体功能、蛋白酶体、凋亡和代谢。有趣的是，我们还发现破坏终末上皮中几个相关途径的基因会导致雄性生育障碍。此外，我们还发现了终末上皮衰老过程中的一系列年龄偏向基因和伪时间轨迹介导的状态偏向基因。终末上皮衰老过程中差异表达的基因主要参与几种常见特征的调控，如线粒体相关事件、蛋白质合成和降解以及代谢过程。我们进一步探讨了果蝇在衰老过程中年龄偏向基因功能限制方面的差异和选择，揭示了2天组上皮细胞中的年龄偏向基因进化迅速，并具有更大的进化优势。scRNA-seq分析揭示了睾丸终末上皮群体的多样性，为进一步系统研究其衰老过程中的功能提供了基因靶点资源。
