小柯机器人

北大汤富酬/乔杰合作描绘胚胎着床的转录和DNA甲基化图谱
2019-08-22 13:44

北京大学汤富酬和北医三院乔杰团队合作,利用单细胞转录组和DNA甲基化组图谱重构人类胚胎着床过程。相关论文于2019年8月22日在线发表在《自然》上。

通过结合着床后人类胚胎发育的体外培养系统和单细胞多组学测序技术,研究人员系统地分析了来自65个人类围着床胚胎的8,000多个体细胞。转录组数据的无监督降维分析和聚类算法显示了上胚层、原始内胚层和滋养外胚层谱系的逐步着床途径,这表明在着床过程中正确建立母-子关系的稳健准备。基于分析着床期间X染色体连锁基因的亲本等位基因特异性表达,雌性胚胎显示随机X染色体失活的启动。值得注意的是,使用单细胞三组学测序分析,显示原始内胚层谱系细胞中基因组的重新甲基化比着床过程中外胚层和滋养外胚层谱系的细胞慢得多,这表明存在在外胚层和原始内胚层的DNA甲基化组中具有不同的重建特征,即使两个谱系都来源于内细胞团。总的来说,这项工作对调节人类胚胎着床的复杂分子机制提供了见解,并有助于推动未来对早期胚胎发育和生殖医学的理解。

据介绍,着床是哺乳动物胚胎发生过程中的里程碑事件。着床失败是人类早期妊娠丢失的重要原因。由于在体内着床后很难获得人类胚胎,目前尚不清楚基因调控网络和表观遗传机制如何控制着床过程。

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汤富酬

汤富酬,北京大学生命科学学院教授。主要研究方向:具有自我更新能力和分化潜能的干细胞是人类胚胎发育过程中以及成年个体生命活动中的关键类型的细胞,对各种干细胞进行深入研究是理解人类发育、生长机制的关键,也是将干细胞应用于临床再生医学、治疗人类疾病的前提。(据北京大学

乔杰

乔杰,医学博士,教授,博士生导师,主任医师,中国工程院院士。现任北京大学第三医院院长,妇产科、生殖医学中心主任。作为世界最大疑难不孕诊治中心和国家自然科学基金委创新群体的带头人,乔杰建立了临床与基础多学科交叉的团队,带领团队年诊治国内外不孕患者近60万人次、实施辅助生殖技术手术3万余例,使中国大陆首例试管婴儿诞生地发展成为国际领先的生殖健康研究与培训基地。(据北京大学第三医院

附:英文原文

Title: Reconstituting the transcriptome and DNA methylome landscapes of human implantation

Author: Fan Zhou, Rui Wang, Peng Yuan, Yixin Ren, Yunuo Mao, Rong Li, Ying Lian, Junsheng Li, Lu Wen, Liying Yan, Jie Qiao, Fuchou Tang

Issue&Volume: 2019-08-21

Abstract: Implantation is a milestone event during mammalian embryogenesis. Implantation failure is a considerable cause of early pregnancy loss in humans1. Owing to the difficulty of obtaining human embryos early after implantation in vivo, it remains unclear how the gene regulatory network and epigenetic mechanisms control the implantation process. Here, by combining an in vitro culture system for the development human embryos after implantation and single-cell multi-omics sequencing technologies, more than 8,000 individual cells from 65 human peri-implantation embryos were systematically analysed. Unsupervised dimensionality reduction and clustering algorithms of the transcriptome data show stepwise implantation routes for the epiblast, primitive endoderm and trophectoderm lineages, suggesting robust preparation for the proper establishment of a mother-to-offspring connection during implantation. Female embryos showed initiation of random X chromosome inactivation based on analysis of parental allele-specific expression of X-chromosome-linked genes during implantation. Notably, using single-cell triple omics sequencing analysis, the re-methylation of the genome in cells from the primitive endoderm lineage was shown to be much slower than in cells of both epiblast and trophectoderm lineages during the implantation process, which indicates that there are distinct re-establishment features in the DNA methylome of the epiblast and primitive endodermeven though both lineages are derived from the inner cell mass. Collectively, our work provides insights into the complex molecular mechanisms that regulate the implantation of human embryos, and helps to advance future efforts to understanding early embryonic development and reproductive medicine.

DOI: 10.1038/s41586-019-1500-0

Source:https://www.nature.com/articles/s41586-019-1500-0

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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