CAS Key Laboratory of Genomic and Precision Medicine, 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, Beijing, 100101, China.
Center for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Nat Commun. 2023 Jan 19;14(1):315. doi: 10.1038/s41467-023-35958-7.
N-methyladenosine (mA) has been demonstrated to regulate RNA metabolism and various biological processes, including gametogenesis and embryogenesis. However, the landscape and function of mA at single cell resolution have not been extensively studied in mammalian oocytes or during pre-implantation. In this study, we developed a single-cell mA sequencing (scmA-seq) method to simultaneously profile the mA methylome and transcriptome in single oocytes/blastomeres of cleavage-stage embryos. We found that mA deficiency leads to aberrant RNA clearance and consequent low quality of Mettl3 conditional knockout (cKO) oocytes. We further revealed that mA regulates the translation and stability of modified RNAs in metaphase II (MII) oocytes and during oocyte-to-embryo transition, respectively. Moreover, we observed mA-dependent asymmetries in the epi-transcriptome between the blastomeres of two-cell embryo. scmA-seq thus allows in-depth investigation into mA characteristics and functions, and the findings provide invaluable single-cell resolution resources for delineating the underlying mechanism for gametogenesis and early embryonic development.
N6-甲基腺苷（m6A）已被证明可调节 RNA 代谢和各种生物学过程，包括配子发生和胚胎发生。然而，在哺乳动物卵母细胞或着床前阶段，尚未广泛研究 m6A 在单细胞分辨率下的全景和功能。在这项研究中，我们开发了一种单细胞 m6A 测序（scmA-seq）方法，可在卵母细胞或卵裂期胚胎的单个卵裂球中同时对 m6A 甲基组和转录组进行分析。我们发现，m6A 缺乏会导致 RNA 清除异常，从而导致 Mettl3 条件性敲除（cKO）卵母细胞质量降低。我们进一步揭示了 m6A 分别在中期 II（MII）卵母细胞和卵母细胞到胚胎转变过程中调节修饰 RNA 的翻译和稳定性。此外，我们观察到两细胞胚胎的卵裂球之间 epi-transcriptome 存在 m6A 依赖性不对称性。scmA-seq 因此可以深入研究 m6A 的特征和功能，研究结果为阐明配子发生和早期胚胎发育的潜在机制提供了宝贵的单细胞分辨率资源。
