Single-Cell Transcriptomic Atlas of Primate Ovarian Aging

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 ooc...

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Published in:Cell 2020-02, Vol.180 (3), p.585-600.e19
Main Authors: Wang, Si, Zheng, Yuxuan, Li, Jingyi, Yu, Yang, Zhang, Weiqi, Song, Moshi, Liu, Zunpeng, Min, Zheying, Hu, Huifang, Jing, Ying, He, Xiaojuan, Sun, Liang, Ma, Lifang, Esteban, Concepcion Rodriguez, Chan, Piu, Qiao, Jie, Zhou, Qi, Izpisua Belmonte, Juan Carlos, Qu, Jing, Tang, Fuchou, Liu, Guang-Hui
Format: Article
Language:English
Subjects:
aging
antioxidant gene
granulosa cell
oocyte
ovary
primate
single-cell RNA sequencing
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Summary: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. [Display omitted] •Single-cell transcriptomic roadmap of NHP ovarian aging•Molecular signatures revealed for NHP oocytes at stepwise developmental stages•Cell-type-specific inactivation of antioxidant genes in aged monkey and human ovaries Single-cell transcriptomic analysis in ovaries of young and old cynomolgus monkeys identifies aging-associated and cell-type-specific dysregulation of antioxidative pathways.
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2020.01.009