Single-cell RNA sequencing reveals transcriptomic landscape and potential targets for human testicular ageing

作者：Kai Xia, Peng Luo, Jiajie Yu, Siyuan He, Lin Dong, Feng Gao, Xuren Chen, Yunlin Ye, Yong Gao, Yuanchen Ma, Cuifeng Yang, Yadong Zhang, Qiyun Yang, Dayu Han, Xin Feng, Zi Wan, Hongcai Cai, Qiong Ke, Tao Wang, Weiqiang Li, Xiang-An Tu, Xiang-Zhou Sun, Chunhua Deng, Andy Peng Xiang · 发表于：Human Reproduction · 年份：2024 · DOI：10.1093/humrep/deae199 · 被引用次数：35 · 研究领域：Sperm and Testicular Function、Testicular diseases and treatments、Single-cell and spatial transcriptomics

STUDY QUESTION: What is the molecular landscape underlying the functional decline of human testicular ageing? SUMMARY ANSWER: The present study provides a comprehensive single-cell transcriptomic atlas of testes from young and old humans and offers insights into the molecular mechanisms and potential targets for human testicular ageing. WHAT IS KNOWN ALREADY: Testicular ageing is known to cause male age-related fertility decline and hypogonadism. Dysfunction of testicular cells has been considered as a key factor for testicular ageing. STUDY DESIGN, SIZE, DURATION: Human testicular biopsies were collected from three young individuals and three old individuals to perform single-cell RNA sequencing (scRNA-seq). The key results were validated in a larger cohort containing human testicular samples from 10 young donors and 10 old donors. PARTICIPANTS/MATERIALS, SETTING, METHODS: scRNA-seq was used to identify gene expression signatures for human testicular cells during ageing. Ageing-associated changes of gene expression in spermatogonial stem cells (SSCs) and Leydig cells (LCs) were analysed by gene set enrichment analysis and validated by immunofluorescent and functional assays. Cell-cell communication analysis was performed using CellChat. MAIN RESULTS AND THE ROLE OF CHANCE: The single-cell transcriptomic landscape of testes from young and old men was surveyed, revealing age-related changes in germline and somatic niche cells. In-depth evaluation of the gene expression dynamic...