Single-Cell Transcriptome Analysis of Uniparental Embryos Reveals Parent-of-Origin Effects on Human Preimplantation Development

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  • Lizhi Leng, Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha 410078, China; Key Laboratory of Reproductive and Stem Cell Engineering, Ministry of Health, Changsha 410078, China; Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha 410078, China.
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  • Jiya Sun, Center of System Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China; Suzhou Institute of Systems Medicine, Suzhou 215123, China.
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  • Jinrong Huang
  • Fei Gong, Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha 410078, China; Key Laboratory of Reproductive and Stem Cell Engineering, Ministry of Health, Changsha 410078, China; Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha 410078, China.
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  • Ling Yang, BGI-Shenzhen, Shenzhen 518083, China; China National GeneBank, BGI-Shenzhen, Shenzhen 518120, China; Lars Bolund Institute of Regenerative Medicine, BGI-Qingdao, BGI-Shenzhen, Qingdao 266555, China.
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  • Shuoping Zhang, Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha 410078, China.
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  • Xuye Yuan, Center of System Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China; Suzhou Institute of Systems Medicine, Suzhou 215123, China.
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  • Fang Fang, BGI-Shenzhen, Shenzhen 518083, China; China National GeneBank, BGI-Shenzhen, Shenzhen 518120, China.
  • ,
  • Xun Xu, BGI-Shenzhen, Shenzhen 518083, China; China National GeneBank, BGI-Shenzhen, Shenzhen 518120, China.
  • ,
  • Yonglun Luo
  • Lars Bolund
  • Brock A Peters, BGI-Shenzhen, Shenzhen 518083, China; China National GeneBank, BGI-Shenzhen, Shenzhen 518120, China; Advanced Genomics Technology Lab, Complete Genomics, Inc., 2904 Orchard Parkway, San Jose, CA 95134, USA.
  • ,
  • Guangxiu Lu, Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha 410078, China; Key Laboratory of Reproductive and Stem Cell Engineering, Ministry of Health, Changsha 410078, China; Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha 410078, China; National Engineering and Research Center of Human Stem Cells, Changsha 410078, China.
  • ,
  • Taijiao Jiang, Center of System Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China; Suzhou Institute of Systems Medicine, Suzhou 215123, China. Electronic address: taijiao@ibms.pumc.edu.cn.
  • ,
  • Fengping Xu, BGI-Shenzhen, Shenzhen 518083, China; China National GeneBank, BGI-Shenzhen, Shenzhen 518120, China; Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, 2100 Copenhagen, Denmark; Lars Bolund Institute of Regenerative Medicine, BGI-Qingdao, BGI-Shenzhen, Qingdao 266555, China. Electronic address: xufengping@genomics.cn.
  • ,
  • Ge Lin, Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha 410078, China; Key Laboratory of Reproductive and Stem Cell Engineering, Ministry of Health, Changsha 410078, China; Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha 410078, China; National Engineering and Research Center of Human Stem Cells, Changsha 410078, China. Electronic address: linggf@hotmail.com.

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.

OriginalsprogEngelsk
TidsskriftCell Stem Cell
Vol/bind25
Nummer5
Sider (fra-til)697-712.e6
ISSN1934-5909
DOI
StatusUdgivet - 7 nov. 2019

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