Zhao Zheng-Hui, Meng Tie-Gang, Chen Xue-Ying, Gao Fei, Schatten Heide, Ou Xiang-Hong, Sun Qing-Yuan
Guangzhou Key Laboratory of Metabolic Diseases and Reproductive Health, Guangdong-Hong Kong Metabolism & Reproduction Joint Laboratory, Reproductive Medicine Center, Guangdong Second Provincial General Hospital, Guangzhou, China.
Medical College, Jinan University, Guangzhou, China.
Commun Biol. 2025 Jun 3;8(1):849. doi: 10.1038/s42003-025-08277-4.
Characterization of cellular heterogeneity and molecular diversity greatly enhances our understanding of the ovary differentiation process. However, regional specification remains largely unexplored during ovary development. Here, we combine spatial transcriptomics and single-cell RNA sequencing to build a spatiotemporal developmental atlas of ovaries from the fetal stage through adulthood. We construct the developmental trajectory of female germ cells and identify key genes essential for primordial follicle assembly. Specifically, we characterize the regional heterogeneity of granulosa cell subtypes contributing to the folliculogenesis, and analyze the molecular distinctions between healthy and atretic follicles. Notably, we discover that Onecut2-positive luteal cells exhibit a specific spatial distribution. Furthermore, lineage tracing reveals that these Onecut2-positive luteal cells originate from Foxl2-positive granulosa cells and Cyp17a1-positive theca cells. Collectively, this study provides a comprehensive delineation of ovary development and regional specificity of ovarian cell types.
细胞异质性和分子多样性的表征极大地增进了我们对卵巢分化过程的理解。然而，在卵巢发育过程中，区域特化在很大程度上仍未得到探索。在这里，我们结合空间转录组学和单细胞RNA测序，构建了从胎儿期到成年期卵巢的时空发育图谱。我们构建了雌性生殖细胞的发育轨迹，并鉴定了原始卵泡组装所必需的关键基因。具体而言，我们表征了参与卵泡发生的颗粒细胞亚型的区域异质性，并分析了健康卵泡和闭锁卵泡之间的分子差异。值得注意的是，我们发现Onecut2阳性黄体细胞呈现出特定的空间分布。此外，谱系追踪显示这些Onecut2阳性黄体细胞起源于Foxl2阳性颗粒细胞和Cyp17a1阳性卵泡膜细胞。总的来说，这项研究全面描绘了卵巢发育以及卵巢细胞类型的区域特异性。
