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Single-Cell Transcriptomic Atlas of Primate Ovarian Aging. 2020
Si Wang, and
Yuxuan Zheng, and
Jingyi Li, and
Yang Yu, and
Weiqi Zhang, and
Moshi Song, and
Zunpeng Liu, and
Zheying Min, and
Huifang Hu, and
Ying Jing, and
Xiaojuan He, and
Liang Sun, and
Lifang Ma, and
Concepcion Rodriguez Esteban, and
Piu Chan, and
Jie Qiao, and
Qi Zhou, and
Juan Carlos Izpisua Belmonte, and
Jing Qu, and
Fuchou Tang, and
Guang-Hui Liu
State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; Beijing Institute for Brain Disorders, Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing 100053, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Molecular mechanisms of ovarian aging and female age-related fertility decline remain unclear. We surveyed the single-cell transcriptomic landscape of ovaries from young and aged non-human primates (NHPs) and identified seven ovarian cell types with distinct gene-expression signatures, including oocyte and six types of ovarian somatic cells. In-depth dissection of gene-expression dynamics of oocytes revealed four subtypes at sequential and stepwise developmental stages. Further analysis of cell-type-specific aging-associated transcriptional changes uncovered the disturbance of antioxidant signaling specific to early-stage oocytes and granulosa cells, indicative of oxidative damage as a crucial factor in ovarian functional decline with age. Additionally, inactivated antioxidative pathways, increased reactive oxygen species, and apoptosis were observed in granulosa cells from aged women. This study provides a comprehensive understanding of the cell-type-specific mechanisms underlying primate ovarian aging at single-cell resolution, revealing new diagnostic biomarkers and potential therapeutic targets for age-related human ovarian disorders.
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