Single-Cell Transcriptome Analysis of Uniparental Embryos Reveals Parent-of-Origin Effects on Human Preimplantation Development
Single-Cell Transcriptome Analysis of Uniparental Embryos Reveals Parent-of-Origin Effects on Human Preimplantation Development
复制标题
单亲胚胎的单细胞转录组分析揭示了亲本对人类植入前发育的影响
DOI：
10.1016/j.stem.2019.09.004
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发表时间：
2019-11-07
期刊：
影响因子：
23.9
通讯作者：
Lin, Ge
中科院分区：
文献类型：
--
作者：
Leng, Lizhi;Sun, Jiya;Lin, Ge
为了研究亲本基因组对早期胚胎发生的贡献，我们系统地分析了人类双亲和单亲胚胎从单细胞到桑椹胚阶段的单细胞转录组。我们观察到单亲胚胎表现出可变且减少的胚胎基因组激活（EGA）。比较转录组分析确定了植入前阶段的 807 个母系偏向表达基因 (MBG) 和 581 个父系偏向表达基因 (PBG)。 MBG 在 4 细胞阶段变得明显，并有助于 EGA 的启动，而 PBG 优先出现在 8 细胞阶段，可能影响胚胎压实和滋养外胚层规格。调控网络分析表明DUX4、EGR2和DUXA是MBGs表达的关键转录因子； ZNF263 和 KLF3 对于 PBG 的表达很重要。我们证明亲本特异性 DNA 甲基化可能解释了大多数 PBG 的表达。我们的结果为了解亲本基因组激活提供了宝贵的资源，并可能有助于阐明亲本对人类早期发育的影响。
To investigate the contribution of parental genomes to early embryogenesis, we profiled the single-cell transcriptomes of human biparental and uniparental embryos systematically from the 1-cell to the morula stage. We observed that uniparental embryos exhibited variable and decreased embryonic genome activation (EGA). Comparative transcriptome analysis identified 807 maternally biased expressed genes (MBGs) and 581 paternally biased expressed genes (PBGs) in the preimplantation stages. MBGs became apparent at the 4-cell stage and contributed to the initiation of EGA, whereas PBGs preferentially appeared at the 8-cell stage and might affect embryo compaction and trophectoderm specification. Regulatory network analysis revealed that DUX4, EGR2, and DUXA are key transcription factors in MBGs' expression; ZNF263 and KLF3 are important for PBGs' expression. We demonstrated that parent-specific DNA methylation might account for the expression of most PBGs. Our results provide a valuable resource to understand parental genome activation and might help to elucidate parent-of-origin effects in early human development.