Single-cell DNA methylome sequencing of human preimplantation embryos

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DNA methylation is a crucial layer of epigenetic regulation during mammalian embryonic development1,2,3. Although the DNA methylome of early human embryos has been analyzed4,5,6, some of the key features have not been addressed thus far. Here we performed single-cell DNA methylome sequencing for human preimplantation embryos and found that tens of thousands of genomic loci exhibited de novo DNA methylation. This finding indicates that genome-wide DNA methylation reprogramming during preimplantation development is a dynamic balance between strong global demethylation and drastic focused remethylation. Furthermore, demethylation of the paternal genome is much faster and thorough than that of the maternal genome. From the two-cell to the postimplantation stage, methylation of the paternal genome is consistently lower than that of the maternal genome. We also show that the genetic lineage of early blastomeres can be traced by DNA methylation analysis. Our work paves the way for deciphering the secrets of DNA methylation reprogramming in early human embryos.

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We thank W. Guo for his insightful discussion. L.Y., J.Q., and F.T. were supported by grants from the National Natural Science Foundation of China (81561138005, 31230047, 31522034, 31571544, 81521002, and 31625018) and the National Basic Research Program of China (2014CB943200 and 2017YFA0102702). J.Q. and F.T. were also supported by a grant from the Beijing Municipal Science and Technology Commission (D151100002415000). L.Y. was supported by a grant from the National High-Technology Research and Development Program (2015AA020407). The work was supported by the Beijing Advanced Innovation Center for Genomics at Peking University.

Author information

Author notes

    • Ping Zhu

    Present address: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China

    • Hongshan Guo

    Present address: Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA, USA

  1. Ping Zhu, Hongshan Guo, Yixin Ren and Yu Hou contributed equally to this work.


  1. Beijing Advanced Innovation Center for Genomics, College of Life Sciences, Department of Obstetrics and Gynecology, Third Hospital, Peking University, Beijing, China

    • Ping Zhu
    • , Hongshan Guo
    • , Yixin Ren
    • , Yu Hou
    • , Ji Dong
    • , Rong Li
    • , Ying Lian
    • , Xiaoying Fan
    • , Boqiang Hu
    • , Yun Gao
    • , Xiaoye Wang
    • , Yuan Wei
    • , Ping Liu
    • , Jie Yan
    • , Xiulian Ren
    • , Peng Yuan
    • , Yifeng Yuan
    • , Zhiqiang Yan
    • , Lu Wen
    • , Liying Yan
    • , Jie Qiao
    •  & Fuchou Tang
  2. Biomedical Institute for Pioneering Investigation via Convergence and Center for Reproductive Medicine, College of Life Sciences, Department of Obstetrics and Gynecology, Third Hospital, Peking University, Beijing, China

    • Ping Zhu
    • , Hongshan Guo
    • , Yu Hou
    • , Ji Dong
    • , Xiaoying Fan
    • , Boqiang Hu
    • , Yun Gao
    • , Lu Wen
    • , Liying Yan
    • , Jie Qiao
    •  & Fuchou Tang
  3. Key Laboratory of Assisted Reproduction and Key Laboratory of Cell Proliferation and Differentiation, Ministry of Education, Beijing, China

    • Yixin Ren
    • , Rong Li
    • , Ying Lian
    • , Xiaoye Wang
    • , Yuan Wei
    • , Ping Liu
    • , Jie Yan
    • , Xiulian Ren
    • , Peng Yuan
    • , Yifeng Yuan
    • , Zhiqiang Yan
    • , Liying Yan
    • , Jie Qiao
    •  & Fuchou Tang
  4. Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China

    • Liying Yan
    •  & Jie Qiao
  5. Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China

    • Jie Qiao
    •  & Fuchou Tang
  6. Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China

    • Ping Zhu
    • , Jie Qiao
    •  & Fuchou Tang


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F.T., J.Q., and L.Y. conceived the project. H.G., Y.R., Y.H., R.L., Y.L., X.F., Y.G., X.W., Y.W., P.L., J.Y., X.R., P.Y., Y.Y., Z.Y. and L.W. performed the experiments. P.Z., J.D., B.H. and H.G. conducted the bioinformatic analyses. F.T., J.Q., L.Y., H.G., P.Z., Y.R. and Y.H. wrote the manuscript with help from all of the authors.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Liying Yan or Jie Qiao or Fuchou Tang.

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