Wang Xiaoyan, Cheng Liping, Lu Xiaojian, Jin He, Cui Lina, Guo Yifei, Guo Jingtao, Xu Eugene Yujun
Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China.
State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, Jiangsu, China; The Third Affiliated Hospital of Shenzhen University - Shenzhen Luohu District People's Hospital, Shenzhen, Guangdong, China.
Cell Rep. 2025 Jan 28;44(1):115118. doi: 10.1016/j.celrep.2024.115118. Epub 2024 Dec 30.
In male animals, spermatogonia in testes differentiate into sperm, one of the most diverse cell types across species. Despite the evolutionary retention of key genes essential for spermatogenesis, the extent of their conservation remains unclear. To explore the genetic basis of spermatogenesis under strong selective pressure, we compare single-cell RNA sequencing (scRNA-seq) datasets from the testes of humans, mice, and fruit flies. Our analysis identifies conserved genes involved in key molecular programs, such as post-transcriptional regulation, meiosis, and energy metabolism. We perform gene knockout experiments of 20 candidate genes, three of which, when mutated in fruit flies, result in reduced male fertility, emphasizing the conservation of sperm centriole and steroid lipid processes across mammals and Drosophila. Additionally, deep-learning analysis uncovers potential transcriptional mechanisms driving gene-expression evolution. These findings establish a core genetic foundation for spermatogenesis, offering insights into sperm-phenotype evolution and the underlying mechanisms of male infertility.
在雄性动物中，睾丸中的精原细胞分化为精子，精子是跨物种最多样化的细胞类型之一。尽管精子发生所必需的关键基因在进化过程中得以保留，但其保守程度仍不清楚。为了探索在强选择压力下精子发生的遗传基础，我们比较了来自人类、小鼠和果蝇睾丸的单细胞RNA测序（scRNA-seq）数据集。我们的分析确定了参与关键分子程序的保守基因，如转录后调控、减数分裂和能量代谢。我们对20个候选基因进行了基因敲除实验，其中三个基因在果蝇中发生突变时会导致雄性生育力下降，这强调了精子中心粒和类固醇脂质过程在哺乳动物和果蝇中的保守性。此外，深度学习分析揭示了驱动基因表达进化的潜在转录机制。这些发现为精子发生奠定了核心遗传基础，为精子表型进化和男性不育的潜在机制提供了见解。
