中国科学院动物研究所的刘光慧、曲静、北京大学汤富酬教授以及美国索尔克生物研究所Juan Carlos Izpisua Belmonte等研究人员合作绘制了灵长类卵巢衰老的单细胞转录组图谱。该研究成果1月30日在线发表在《细胞》上。
研究人员调查了年轻人和老年人的非人类灵长类动物（NHP）卵巢的单细胞转录组情况，并鉴定了七种具有不同基因表达特征的卵巢细胞，包括卵母细胞和六种类型的卵巢体细胞。卵母细胞基因表达动态的深入解剖揭示了在顺序和逐步发展阶段的四个亚型。细胞类型特异性衰老相关转录变化的进一步分析揭示了早期卵母细胞和颗粒细胞特有的抗氧化剂信号传导的紊乱，表明氧化损伤是卵巢功能下降的关键因素。此外，在老年妇女的颗粒细胞中观察到失活的抗氧化途径、活性氧增加和凋亡。这项研究以单细胞分辨率全面了解了灵长类动物卵巢衰老背后的细胞类型特异性机制，揭示了新的诊断性生物标记物以及与年龄相关人类卵巢疾病的潜在治疗靶标。
据悉，卵巢衰老和女性与年龄相关的生育力下降的分子机制仍不清楚。
附：英文原文
Title: Single-Cell Transcriptomic Atlas of Primate Ovarian Aging
Author: Si Wang, Yuxuan Zheng, Jingyi Li, Yang Yu, Weiqi Zhang, Moshi Song, Zunpeng Liu, Zheying Min, Huifang Hu, Ying Jing, Xiaojuan He, Liang Sun, Lifang Ma, Concepcion Rodriguez Esteban, Piu Chan, Jie Qiao, Qi Zhou, Juan Carlos Izpisua Belmonte, Jing Qu, Fuchou Tang, Guang-Hui Liu
Issue&Volume: January 30, 2020
Abstract: Molecular mechanisms of ovarian aging and female age-related fertility decline remainunclear. We surveyed the single-cell transcriptomic landscape of ovaries from youngand aged non-human primates (NHPs) and identified seven ovarian cell types with distinctgene-expression signatures, including oocyte and six types of ovarian somatic cells.In-depth dissection of gene-expression dynamics of oocytes revealed four subtypesat sequential and stepwise developmental stages. Further analysis of cell-type-specificaging-associated transcriptional changes uncovered the disturbance of antioxidantsignaling specific to early-stage oocytes and granulosa cells, indicative of oxidativedamage as a crucial factor in ovarian functional decline with age. Additionally, inactivatedantioxidative pathways, increased reactive oxygen species, and apoptosis were observedin granulosa cells from aged women. This study provides a comprehensive understandingof the cell-type-specific mechanisms underlying primate ovarian aging at single-cellresolution, revealing new diagnostic biomarkers and potential therapeutic targetsfor age-related human ovarian disorders.
DOI: 10.1016/j.cell.2020.01.009
Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30056-8