TY - JOUR A1 - Xu, Jiawei A1 - Shu, Yimin A1 - Yao, Guidong A1 - Zhang, Yu A1 - Niu, Wenbin A1 - Zhang, Yile A1 - Ma, Xueshan A1 - Jin, Haixia A1 - Zhang, Fuli A1 - Shi, Senlin A1 - Wang, Yang A1 - Song, Wenyan A1 - Dai, Shanjun A1 - Cheng, Luyao A1 - Zhang, Xiangyang A1 - Xie, Wei A1 - Hsueh, Aaron J. A1 - Sun, Yingpu T1 - Parental methylome reprogramming in human uniparental blastocysts reveals germline memory transition Y1 - 2021/09/01 JF - Genome Research JO - Genome Research SP - 1519 EP - 1530 DO - 10.1101/gr.273318.120 VL - 31 IS - 9 UR - http://genome.cshlp.org/content/31/9/1519.abstract N2 - 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. ER -