Zhao Bingru, Dai Keke, Li Shanglai, Zhang Guomin, Lv Wenli, Liu Wanru, Cai Yu, Wang Feng, Zhou Huaijun, Guan Dailu, Zhang Yanli
Jiangsu Livestock Embryo Engineering Laboratory, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu 210095, China.
Department of Animal Science, University of California, Davis, Davis, CA 95616, USA.
iScience. 2025 Apr 14;28(5):112422. doi: 10.1016/j.isci.2025.112422. eCollection 2025 May 16.
Sheep () are valuable biomedical models for studying human reproductive biology, however, the transcriptional dynamics underlying their ovarian development remain insufficiently characterized. In this study, we profiled 61,649 single-cell transcriptomes from sheep ovarian tissues across key developmental stages: prenatal (E90), pre-puberty (M3), post-puberty (M6), and adulthood (Y2, Y4). We identified nine major cell types with distinct and dynamic gene expression patterns, highlighting significant developmental transitions. Notably, granulosa cells exhibited profound transcriptomic shifts, underscoring their critical role in oocyte maturation and follicular development. Key transcription factors, such as FOXO1 and ESR1, were identified as potential drivers of these transitions. Further cross-species comparisons revealed strong conservation in cell types, composition, and gene expression networks between sheep and human developing ovaries. Leveraging these conserved features, we uncovered context-dependent (e.g., cell-type-specific, developmental-stage-specific) associations with human reproductive traits and diseases. These findings advance our understanding of ovarian development in sheep and reinforce their utility as translational models in reproductive biology and disease research.
绵羊是研究人类生殖生物学的重要生物医学模型，然而，其卵巢发育的转录动态仍未得到充分表征。在本研究中，我们对绵羊卵巢组织在关键发育阶段（产前（E90）、青春期前（M3）、青春期后（M6）和成年期（Y2、Y4））的61,649个单细胞转录组进行了分析。我们鉴定出了九种主要细胞类型，它们具有独特且动态的基因表达模式，突出了显著的发育转变。值得注意的是，颗粒细胞表现出深刻的转录组变化，强调了它们在卵母细胞成熟和卵泡发育中的关键作用。关键转录因子，如FOXO1和ESR1，被确定为这些转变的潜在驱动因素。进一步的跨物种比较揭示了绵羊和人类发育中的卵巢在细胞类型、组成和基因表达网络方面的高度保守性。利用这些保守特征，我们发现了与人类生殖性状和疾病的上下文依赖性（如细胞类型特异性、发育阶段特异性）关联。这些发现增进了我们对绵羊卵巢发育的理解，并加强了它们作为生殖生物学和疾病研究中转译模型的效用。
