Single-cell multi-omic analysis profiles defective genome activation and epigenetic reprogramming associated with human pre-implantation embryo arrest.
Single-cell multi-omic analysis profiles defective genome activation and epigenetic reprogramming associated with human pre-implantation embryo arrest.
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DOI：
10.1016/j.celrep.2023.112100
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发表时间：
2023-02
期刊：
影响因子：
8.8
通讯作者：
J. R. Hernández Mora;Claudia Buhigas;Stephen J. Clark;R. Del Gallego Bonilla;Dagne Daskeviciute;Ana Monteagudo-Sánchez;M. E. Poo-Llanillo;J. Medrano;C. Simón;M. Meseguer;G. Kelsey;D. Monk
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文献类型：
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作者：
J. R. Hernández Mora;Claudia Buhigas;Stephen J. Clark;R. Del Gallego Bonilla;Dagne Daskeviciute;Ana Monteagudo-Sánchez;M. E. Poo-Llanillo;J. Medrano;C. Simón;M. Meseguer;G. Kelsey;D. Monk
在哺乳动物发育的植入前阶段，母体储存的物质会促进精子和卵母细胞表观遗传特征的消除，并负责伴随的基因组激活。在这里，我们利用单细胞甲基化组和转录组测序 (scM&T-seq) 以单细胞分辨率量化卵母细胞和一系列发育人类胚胎中的 mRNA 表达和 DNA 甲基化。我们全面描述了胚胎基因组激活和母体转录降解的特征，并绘制了发育高质量胚胎中关键的表观遗传重编程事件。通过将这些特征与延时成像确定的经历自发卵裂阶段停滞的早期胚胎进行比较，我们识别出未能适当激活其基因组或进行表观遗传重编程的胚胎。我们的结果表明，未能成功实现这些重要的里程碑会阻碍植入前胚胎的发育潜力，并且可能对辅助生殖周期的成功产生类似于非整倍性的重要影响。
During pre-implantation stages of mammalian development, maternally stored material promotes both the erasure of the sperm and oocyte epigenetic profiles and is responsible for concomitant genome activation. Here, we have utilized single-cell methylome and transcriptome sequencing (scM&T-seq) to quantify both mRNA expression and DNA methylation in oocytes and a developmental series of human embryos at single-cell resolution. We fully characterize embryonic genome activation and maternal transcript degradation and map key epigenetic reprogramming events in developmentally high-quality embryos. By comparing these signatures with early embryos that have undergone spontaneous cleavage-stage arrest, as determined by time-lapse imaging, we identify embryos that fail to appropriately activate their genomes or undergo epigenetic reprogramming. Our results indicate that a failure to successfully accomplish these essential milestones impedes the developmental potential of pre-implantation embryos and is likely to have important implications, similar to aneuploidy, for the success of assisted reproductive cycles.