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灵长类卵巢衰老的单细胞转录图谱

Si Wang ¹, Yuxuan Zheng ², Jingyi Li ³

¹State 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.
²Beijing Advanced Innovation Center for Genomics, College of Life Sciences, Peking University, Beijing 100871, China; Biomedical Institute for Pioneering Investigation via Convergence, Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing 100871, China; Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.
³State Key Laboratory of Membrane 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.
⁴Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, Beijing 100191, China; Stem Cell Research Center, Peking University Third Hospital, Beijing 100191, China.
⁵National 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; Institute for Stem cell and Regeneration, CAS, Beijing 100101, China; Disease Genomics and Individualized Medicine Laboratory, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
⁶State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; Institute for Stem cell and Regeneration, CAS, Beijing 100101, China.
⁷State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
⁸Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, Beijing 100191, China.
⁹Beijing 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.
¹⁰The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing 100730, China.
¹¹Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California, United States of America.
¹²State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; Institute for Stem cell and Regeneration, CAS, Beijing 100101, China.
¹³State Key Laboratory of Membrane 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; Institute for Stem cell and Regeneration, CAS, Beijing 100101, China.

⁰State 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.

Cell +

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2020年二月1日

在PubMed上查看摘要

概括

卵巢衰老和生育能力下降与氧化损伤有关,特别是在卵细胞和粒状细胞中. 这项研究揭示了与年龄相关的生育问题的分子机制和潜在治疗点.

科学领域

生殖生物学
老年学
基因组学

背景情况

女人的生育能力随着年龄的增长而下降,这是由于对卵巢衰老机制的了解不足.
卵巢衰老会影响卵细胞质量和体细胞功能.

研究的目的

阐明卵巢衰老和与年龄相关的生育能力下降的分子机制.
通过单细胞转录组学来识别老化的卵巢中的细胞类型特异性变化.

主要方法

从年轻和老年非人类灵长类动物 (NHPs) 的卵巢单细胞RNA测序.
鉴定和描述七种不同的卵巢细胞类型.
对基因表达动态和与衰老相关的转录变化的分析.

主要成果

包括卵细胞和体细胞在内的七种卵巢细胞类型具有独特的基因表达特征.
卵细胞发育阶段根据基因表达被划分为四个亚型.
从老年NHP中观察到早期卵细胞和粒状细胞的抗氧化信号和氧化损伤.
在老年妇女的粒状细胞中证实了抗氧化途径的失活,活性氧物种的增加和亡.

结论

氧化损伤是灵长类卵巢衰老和生育能力下降的一个关键因素.
已确定导致卵巢衰老的细胞类型特异性分子机制.
这些发现可能会为与年龄相关的人类卵巢疾病提供新的诊断生物标志物和治疗点.

关键词:

年龄增长抗氧化基因颗粒细胞卵子细胞卵巢灵长类动物单细胞RNA测序

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