Ge Wei, Niu Yi-Lin, Li Yu-Kang, Li Li, Wang Han, Li Wen-Wen, Qiao Tian, Feng Yan-Ni, Feng Yu-Qing, Liu Jing, Wang Jun-Jie, Sun Xiao-Feng, Cheng Shun-Feng, Li Lan, Shen Wei
College of Life Sciences, Key Laboratory of Animal Reproduction and Biotechnology in Universities of Shandong, Qingdao Agricultural University, Qingdao, 266109, China.
Laboratory of Animal Reproductive Physiology and Disease, College of Veterinary Medicine, Qingdao Agricultural University, Qingdao, 266109, China.
Genome Biol. 2025 Jan 2;26(1):2. doi: 10.1186/s13059-024-03464-8.
In humans and other mammals, the process of oogenesis initiates asynchronously in specific ovarian regions, leading to the localization of dormant and growing follicles in the cortex and medulla, respectively; however, the current understanding of this process remains insufficient.
Here, we integrate single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) to comprehend spatial-temporal gene expression profiles and explore the spatial organization of ovarian microenvironments during early oogenesis in pigs. Projection of the germ cell clusters at different stages of oogenesis into the spatial atlas unveils a "cortical to medullary (C-M)" distribution of germ cells in the developing porcine ovaries. Cross-species analysis between pigs and humans unveils a conserved C-M distribution pattern of germ cells during oogenesis, highlighting the utility of pigs as valuable models for studying human oogenesis in a spatial context. RNA velocity analysis with ST identifies the molecular characteristics and spatial dynamics of granulosa cell lineages originating from the cortical and medullary regions in pig ovaries. Spatial co-occurrence analysis and intercellular communication analysis unveils a distinct cell-cell communication pattern between germ cells and somatic cells in the cortex and medulla regions. Notably, in vitro culture of ovarian tissues verifies that intercellular NOTCH signaling and extracellular matrix (ECM) proteins played crucial roles in initiating meiotic and oogenic programs, highlighting an underappreciated role of ovarian microenvironments in orchestrating germ cell fates.
Overall, our work provides insight into the spatial characteristics of early oogenesis and the regulatory role of ovarian microenvironments in germ cell fate within a spatial context.
在人类和其他哺乳动物中，卵子发生过程在特定的卵巢区域异步启动，导致休眠卵泡和生长卵泡分别定位于皮质和髓质；然而，目前对这一过程的了解仍然不足。
在这里，我们整合单细胞RNA测序（scRNA-seq）和空间转录组学（ST），以了解时空基因表达谱，并探索猪早期卵子发生过程中卵巢微环境的空间组织。将卵子发生不同阶段的生殖细胞簇投影到空间图谱中，揭示了发育中的猪卵巢中生殖细胞的“皮质到髓质（C-M）”分布。猪和人类之间的跨物种分析揭示了卵子发生过程中生殖细胞保守的C-M分布模式，突出了猪作为在空间背景下研究人类卵子发生的有价值模型的实用性。利用ST进行的RNA速度分析确定了猪卵巢皮质和髓质区域颗粒细胞谱系的分子特征和空间动态。空间共现分析和细胞间通讯分析揭示了皮质和髓质区域生殖细胞与体细胞之间独特的细胞间通讯模式。值得注意的是，卵巢组织的体外培养证实细胞间NOTCH信号和细胞外基质（ECM）蛋白在启动减数分裂和卵子发生程序中起关键作用，突出了卵巢微环境在协调生殖细胞命运中未被充分认识的作用。
总体而言，我们的工作深入了解了早期卵子发生的空间特征以及卵巢微环境在空间背景下对生殖细胞命运的调控作用。
