Spatiotemporal transcriptomic changes of human ovarian aging and the regulatory role of FOXP1

作者：Meng Wu, Weicheng Tang, Ying Chen, Liru Xue, Jun Dai, Yan Li, Yan Li, Xiaoran Zhu, Chuqing Wu, Jiaqiang Xiong, Jinjin Zhang, Tong Wu, Su Zhou, Dan Chen, Chaoyang Sun, Jing Yu, Hongyi Li, Yican Guo, Yibao Huang, Qingqing Zhu, Simin Wei, Ziliang Zhou, Mingfu Wu, Ya Li, Ya Li, Tao Xiang, Huiying Qiao, Shixuan Wang · 发表于：Nature Aging · 年份：2024 · DOI：10.1038/s43587-024-00607-1 · 被引用次数：131 · 研究领域：Single-cell and spatial transcriptomics、Reproductive Biology and Fertility、Genetics, Aging, and Longevity in Model Organisms

Limited understanding exists regarding how aging impacts the cellular and molecular aspects of the human ovary. This study combines single-cell RNA sequencing and spatial transcriptomics to systematically characterize human ovarian aging. Spatiotemporal molecular signatures of the eight types of ovarian cells during aging are observed. An analysis of age-associated changes in gene expression reveals that DNA damage response may be a key biological pathway in oocyte aging. Three granulosa cells subtypes and five theca and stromal cells subtypes, as well as their spatiotemporal transcriptomics changes during aging, are identified. FOXP1 emerges as a regulator of ovarian aging, declining with age and inhibiting CDKN1A transcription. Silencing FOXP1 results in premature ovarian insufficiency in mice. These findings offer a comprehensive understanding of spatiotemporal variability in human ovarian aging, aiding the prioritization of potential diagnostic biomarkers and therapeutic strategies.