单细胞m6A测序（scm6A-seq）揭示了卵母细胞成熟和胚胎早期发育过程中单细胞动态m6A修饰图谱

N6-甲基腺苷（m6A）可以调节RNA代谢和各种生物过程，包括配子发生和胚胎发生。然而，哺乳动物卵母细胞或植入前单细胞精度下的m6A修饰图谱和功能尚未得到广泛研究。在本研究中，我们开发了一种单细胞m6A测序（scm6A-seq）方法，以同时分析卵裂期胚胎的单个卵母细胞/卵裂球中的m6A甲基组和转录组。我们发现m6A缺乏会导致异常的RNA清除，从而导致Mettl3Gdf9条件敲除（cKO）卵母细胞的低质量。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的过渡过程中调节修饰RNA的翻译和稳定性。此外，我们在两个细胞胚胎的卵裂球之间的表转录组中观察到m6A依赖性不对称。因此，scm6A-seq可以深入研究m6A的特征和功能，这些发现为描述配子发生和早期胚胎发育的潜在机制提供了重要的单细胞精度下新的研究维度。

N6-methyladenosine (m6A) regulates RNA metabolism and various biological processes including gametogenesis and embryogenesis. However, the m6A modification landscapes and functions in mammalian oocytes or at preimplantation stages with single-cell resolution have not been extensively investigated. In this study, we developed a single-cell m6A sequencing (scm6A-seq) approach to simultaneously profile the m6A methylome and transcriptome in individual oocytes or blastomeres from cleavage-stage embryos. We found that loss of m6A induces aberrant RNA clearance, leading to compromised quality of Mettl3Gdf9 conditional knockout (cKO) oocytes. We further revealed that m6A regulates the translation and stability of modified RNAs during metaphase II (MII) oocyte maturation and the oocyte-to-embryo transition, respectively. Moreover, we observed m6A-dependent asymmetry in the epitranscriptome between blastomeres of two-cell embryos. Therefore, scm6A-seq enables in-depth exploration of the characteristics and functions of m6A, and these findings provide a novel single-cell resolution research dimension for deciphering the underlying mechanisms of gametogenesis and early embryonic development.

搜集汇总

背景与挑战

背景概述

该数据集通过单细胞m6A测序技术，揭示了小鼠卵母细胞成熟和早期胚胎发育过程中m6A修饰的动态变化图谱。数据集包含21个样本，涵盖RNA-seq和MeRIP-Seq测序数据，用于同时分析m6A甲基化组和转录组，重点关注m6A在卵母细胞质量、RNA代谢以及胚胎卵裂期不对称性中的调控作用。