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scm6A-seq reveals single-cell landscapes of the dynamic m6A during oocyte maturation and early embryonic development

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Listed:
  • Huan Yao

    (Collaborative Innovation Center of Genetics and Development, College of Future Technology, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation
    Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University)

  • Chun-Chun Gao

    (Collaborative Innovation Center of Genetics and Development, College of Future Technology, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation)

  • Danru Zhang

    (College of Biological Sciences, China Agricultural University)

  • Jiawei Xu

    (The First Affiliated Hospital of Zhengzhou University)

  • Gege Song

    (Collaborative Innovation Center of Genetics and Development, College of Future Technology, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation)

  • Xiu Fan

    (Collaborative Innovation Center of Genetics and Development, College of Future Technology, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation)

  • Dao-Bo Liang

    (Collaborative Innovation Center of Genetics and Development, College of Future Technology, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation)

  • Yu-Sheng Chen

    (Collaborative Innovation Center of Genetics and Development, College of Future Technology, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation)

  • Qian Li

    (Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University)

  • Yanjie Guo

    (Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University)

  • Yu-Ting Cai

    (Collaborative Innovation Center of Genetics and Development, College of Future Technology, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation
    University of Chinese Academy of Sciences)

  • Lulu Hu

    (Shanghai Cancer Center, Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Shanghai Medical College of Fudan University)

  • Yong-Liang Zhao

    (Collaborative Innovation Center of Genetics and Development, College of Future Technology, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation
    University of Chinese Academy of Sciences)

  • Ying-Pu Sun

    (Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University)

  • Ying Yang

    (Collaborative Innovation Center of Genetics and Development, College of Future Technology, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation
    University of Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Jianyong Han

    (College of Biological Sciences, China Agricultural University)

  • Yun-Gui Yang

    (Collaborative Innovation Center of Genetics and Development, College of Future Technology, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation
    University of Chinese Academy of Sciences
    Chinese Academy of Sciences)

Abstract

N6-methyladenosine (m6A) has been demonstrated to regulate RNA metabolism and various biological processes, including gametogenesis and embryogenesis. However, the landscape and function of m6A at single cell resolution have not been extensively studied in mammalian oocytes or during pre-implantation. In this study, we developed a single-cell m6A sequencing (scm6A-seq) method to simultaneously profile the m6A methylome and transcriptome in single oocytes/blastomeres of cleavage-stage embryos. We found that m6A deficiency leads to aberrant RNA clearance and consequent low quality of Mettl3Gdf9 conditional knockout (cKO) oocytes. We further revealed that m6A regulates the translation and stability of modified RNAs in metaphase II (MII) oocytes and during oocyte-to-embryo transition, respectively. Moreover, we observed m6A-dependent asymmetries in the epi-transcriptome between the blastomeres of two-cell embryo. scm6A-seq thus allows in-depth investigation into m6A characteristics and functions, and the findings provide invaluable single-cell resolution resources for delineating the underlying mechanism for gametogenesis and early embryonic development.

Suggested Citation

  • Huan Yao & Chun-Chun Gao & Danru Zhang & Jiawei Xu & Gege Song & Xiu Fan & Dao-Bo Liang & Yu-Sheng Chen & Qian Li & Yanjie Guo & Yu-Ting Cai & Lulu Hu & Yong-Liang Zhao & Ying-Pu Sun & Ying Yang & Jia, 2023. "scm6A-seq reveals single-cell landscapes of the dynamic m6A during oocyte maturation and early embryonic development," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-35958-7
    DOI: 10.1038/s41467-023-35958-7
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    1. Jiadong Liu & Mingwei Gao & Jiangping He & Kaixin Wu & Siyuan Lin & Lingmei Jin & Yaping Chen & He Liu & Junjie Shi & Xiwei Wang & Lei Chang & Yingying Lin & Yu-Li Zhao & Xiaofei Zhang & Man Zhang & G, 2021. "The RNA m6A reader YTHDC1 silences retrotransposons and guards ES cell identity," Nature, Nature, vol. 591(7849), pages 322-326, March.
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    Cited by:

    1. Long Bai & Yu Xiang & Minyue Tang & Shuangying Liu & Qingqing Chen & Qichao Chen & Min Zhang & Shan Wan & Yimiao Sang & Qingfang Li & Sisi Wang & Zhekun Li & Yang Song & Xiaoling Hu & Luna Mao & Guofa, 2023. "ALKBH5 controls the meiosis-coupled mRNA clearance in oocytes by removing the N 6-methyladenosine methylation," Nature Communications, Nature, vol. 14(1), pages 1-21, December.

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