Uniparental embryos derived from only the mother (gynogenetic [GG]) or the father (androgenetic [AG]) are unique models for studying genomic imprinting and parental contributions to embryonic development. Human parthenogenetic embryos can be obtained following artificial activation of unfertilized oocytes, but the production of AG embryos by injection of two sperm into one denucleated oocyte leads to an extra centriole, resulting in multipolar spindles, abnormal cell division, and developmental defects. Here, we improved androgenote production by transferring the male pronucleus from one zygote into another haploid androgenote to prevent extra centrioles and successfully generated human diploid AG embryos capable of developing into blastocysts with an identifiable inner cell mass (ICM) and trophectoderm (TE). The GG embryos were also generated. The zygotic genome was successfully activated in both the AG and GG embryos. DNA methylome analysis showed that the GG blastocysts partially retain the oocyte transcription-dependent methylation pattern, whereas the AG blastocyst methylome showed more extensive demethylation. The methylation states of most known imprinted differentially methylated regions (DMRs) were recapitulated in the AG and GG blastocysts. Novel candidate imprinted DMRs were also identified. The production of uniparental human embryos followed by transcriptome and methylome analysis is valuable for identifying parental contributions and epigenome memory transitions during early human development.

中文翻译：

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人类单亲胚泡中的亲本甲基化组重编程揭示了种系记忆转变

仅来自母亲（雌激素 [GG]）或父亲（雄激素 [AG]）的单亲胚胎是研究基因组印记和父母对胚胎发育的贡献的独特模型。人工激活未受精的卵母细胞可以获得人类孤雌胚胎，但通过将两个精子注射到一个无核卵母细胞中来产生 AG 胚胎会导致额外的中心粒，从而导致多极纺锤体、异常细胞分裂和发育缺陷。在这里，我们通过将雄性原核从一个受精卵转移到另一个单倍体雄激素以防止额外的中心粒来改善雄激素的产生，并成功地产生了能够发育成具有可识别的内细胞团 (ICM) 和滋养外胚层 (TE) 的囊胚的人类二倍体 AG 胚胎。GG胚胎也产生了。合子基因组在 AG 和 GG 胚胎中都被成功激活。DNA甲基化组分析显示GG囊胚部分保留了卵母细胞转录依赖性甲基化模式，而AG囊胚甲基化组表现出更广泛的去甲基化。大多数已知的印记差异甲基化区域（DMR）的甲基化状态在 AG 和 GG 胚泡中得到了概括。还确定了新的候选印记 DMR。单亲人类胚胎的产生以及转录组和甲基化组分析对于识别人类早期发育过程中的亲本贡献和表观基因组记忆转变很有价值。DNA甲基化组分析显示GG囊胚部分保留了卵母细胞转录依赖性甲基化模式，而AG囊胚甲基化组表现出更广泛的去甲基化。大多数已知的印记差异甲基化区域（DMR）的甲基化状态在 AG 和 GG 胚泡中得到了概括。还确定了新的候选印记 DMR。单亲人类胚胎的产生以及转录组和甲基化组分析对于识别人类早期发育过程中的亲本贡献和表观基因组记忆转变很有价值。DNA甲基化组分析显示GG囊胚部分保留了卵母细胞转录依赖性甲基化模式，而AG囊胚甲基化组表现出更广泛的去甲基化。大多数已知的印记差异甲基化区域（DMR）的甲基化状态在 AG 和 GG 胚泡中得到了概括。还确定了新的候选印记 DMR。单亲人类胚胎的产生以及转录组和甲基化组分析对于识别人类早期发育过程中的亲本贡献和表观基因组记忆转变很有价值。还确定了新的候选印记 DMR。单亲人类胚胎的产生以及转录组和甲基化组分析对于识别人类早期发育过程中的亲本贡献和表观基因组记忆转变很有价值。还确定了新的候选印记 DMR。单亲人类胚胎的产生以及转录组和甲基化组分析对于识别人类早期发育过程中的亲本贡献和表观基因组记忆转变很有价值。