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This study employs single-cell RNA sequencing (scRNA-seq) to investigate human spermatogenesis across developmental stages and under pathological conditions, including non-obstructive azoospermia (NOA). The analysis highlights the critical role of Sertoli cells in supporting germ cell development by providing structural support, paracrine factors, and essential nutrients. Pathological conditions, such as NOA and Klinefelter syndrome, reveal significant disruptions in Sertoli cell function, including impaired cell signaling, mitochondrial activity, and transcriptional regulation. These changes are closely linked to defects in germ cell progression and spermatogenic failure. Comparative profiling also identifies stage-specific transcriptional changes in both Sertoli and Leydig cells, uncovering their dynamic interactions with germ cells. This work provides new insights into the cellular and molecular mechanisms of spermatogenesis and identifies potential biomarkers and therapeutic targets, particularly emphasizing the pivotal contributions of Sertoli cells in maintaining testicular homeostasis and fertility.

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scRNA-Seq-Based Transcriptome Profiling and Relevant Bioinformatics Approaches to Uncover Novel Insights in Studying Human Spermatogenesis

  • 章节

  • 发表日期：

    2025年

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  • Xiaolong Wu,
  • Hanchao Liu,
  • Lin Hua,
  • Xintao Gao,
  • Longfei Hu,
  • Lingling Wang,
  • Tiao Bu,
  • Fei Sun,
  • C. Yan Cheng

摘要

This study employs single-cell RNA sequencing (scRNA-seq) to investigate human spermatogenesis across developmental stages and under pathological conditions, including non-obstructive azoospermia (NOA). The analysis highlights the critical role of Sertoli cells in supporting germ cell development by providing structural support, paracrine factors, and essential nutrients. Pathological conditions, such as NOA and Klinefelter syndrome, reveal significant disruptions in Sertoli cell function, including impaired cell signaling, mitochondrial activity, and transcriptional regulation. These changes are closely linked to defects in germ cell progression and spermatogenic failure. Comparative profiling also identifies stage-specific transcriptional changes in both Sertoli and Leydig cells, uncovering their dynamic interactions with germ cells. This work provides new insights into the cellular and molecular mechanisms of spermatogenesis and identifies potential biomarkers and therapeutic targets, particularly emphasizing the pivotal contributions of Sertoli cells in maintaining testicular homeostasis and fertility.