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

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 (), Jianyong Han () and Yun-Gui Yang ()
Additional contact information
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
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
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
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
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

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-35958-7

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