研究繪製靈長類卵巢衰老的單細胞轉錄圖譜
作者:
小柯機器人發布時間:2020/2/12 17:45:56
中國科學院動物研究所的劉光慧、曲靜、北京大學湯富酬教授以及美國索爾克生物研究所Juan Carlos Izpisua Belmonte等研究人員合作繪製了靈長類卵巢衰老的單細胞轉錄組圖譜。該研究成果1月30日在線發表在《細胞》上。
研究人員調查了年輕人和老年人的非人類靈長類動物(NHP)卵巢的單細胞轉錄組情況,並鑑定了七種具有不同基因表達特徵的卵巢細胞,包括卵母細胞和六種類型的卵巢體細胞。卵母細胞基因表達動態的深入解剖揭示了在順序和逐步發展階段的四個亞型。細胞類型特異性衰老相關轉錄變化的進一步分析揭示了早期卵母細胞和顆粒細胞特有的抗氧化劑信號傳導的紊亂,表明氧化損傷是卵巢功能下降的關鍵因素。此外,在老年婦女的顆粒細胞中觀察到失活的抗氧化途徑、活性氧增加和凋亡。這項研究以單細胞解析度全面了解了靈長類動物卵巢衰老背後的細胞類型特異性機制,揭示了新的診斷性生物標記物以及與年齡相關人類卵巢疾病的潛在治療靶標。
據悉,卵巢衰老和女性與年齡相關的生育力下降的分子機制仍不清楚。
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
Cell:《細胞》,創刊於1974年。隸屬於細胞出版社,最新IF:36.216