Single-Cell Transcriptomic Atlas of Primate Ovarian Aging

被引：429

作者：

Wang, Si ^{[1
,3
,4
,5
,7
]}

Zheng, Yuxuan ^{[2
,9
,10
]}

Li, Jingyi ^{[1
,4
,5
,7
]}

Yu, Yang ^{[6
,12
]}

Zhang, Weiqi ^{[4
,5
,7
,8
,13
]}

Song, Moshi ^{[1
,7
,8
]}

Liu, Zunpeng ^{[3
,7
]}

Min, Zheying ^{[6
]}

Hu, Huifang ^{[3
,7
]}

Jing, Ying ^{[3
,7
]}

He, Xiaojuan ^{[5
]}

Sun, Liang ^{[14
]}

Ma, Lifang ^{[6
]}

Esteban, Concepcion Rodriguez ^{[11
]}

Chan, Piu ^{[5
]}

Qiao, Jie ^{[6
]}

Zhou, Qi ^{[3
,7
,8
]}

Belmonte, Juan Carlos Izpisua ^{[11
]}

Qu, Jing ^{[3
,7
,8
]}

Tang, Fuchou ^{[2
,9
,10
]}

Liu, Guang-Hui ^{[1
,4
,5
,7
,8
]}

机构：

[1] Chinese Acad Sci, Inst Zool, State Key Lab Membrane Biol, Beijing 100101, Peoples R China

[2] Peking Univ, Coll Life Sci, Beijing Adv Innovat Ctr Genom, Beijing 100871, Peoples R China

[3] Chinese Acad Sci, Inst Zool, State Key Lab Stem Cell & Reprod Biol, Beijing 100101, Peoples R China

[4] Chinese Acad Sci, CAS Ctr Excellence Biomacromol, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China

[5] Capital Med Univ, Adv Innovat Ctr Human Brain Protect, Natl Clin Res Ctr Geriatr Disorders, Beijing Inst Brain Disorders,Xuanwu Hosp, Beijing 100053, Peoples R China

[6] Peking Univ, Ctr Reprod Med, Dept Obstet & Gynecol, Hosp 3, Beijing 100191, Peoples R China

[7] Univ Chinese Acad Sci, Beijing 100049, Peoples R China

[8] Chinese Acad Sci, Inst Stem Cell & Regenerat, Beijing 100101, Peoples R China

[9] Minist Educ, Key Lab Cell Proliferat & Differentiat, Biomed Inst Pioneering Invest Via Convergence, Beijing 100871, Peoples R China

[10] Peking Univ, Acad Adv Interdisciplinary Studies, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China

[11] Salk Inst Biol Studies, Gene Express Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA

[12] Peking Univ, Stem Cell Res Ctr, Hosp 3, Beijing 100191, Peoples R China

[13] Chinese Acad Sci, Beijing Inst Genom, Dis Genom & Individualized Med Lab, Beijing 100101, Peoples R China

[14] Beijing Hosp, Natl Ctr Gerontol, MOH Key Lab Geriatr, Beijing 100730, Peoples R China

来源：

CELL | 2020年 / 180卷 / 03期

基金：

北京市自然科学基金; 中国国家自然科学基金;

关键词：

GENE-EXPRESSION; ENRICHMENT ANALYSIS; CYNOMOLGUS MONKEYS; GRANULOSA-CELLS; STEM-CELLS; RNA; REVEALS; DIFFERENTIATION; MENOPAUSE; OOCYTES;

D O I：

10.1016/j.cell.2020.01.009

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：585 / +

页数：35

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