PDF(Pubmed)
Abstract：
The oocyte-to-embryo transition (OET) converts terminally differentiated gametes into a totipotent embryo and is critically controlled by maternal mRNAs and proteins, while the genome is silent until zygotic genome activation. How the transcriptome, translatome, and proteome are coordinated during this critical developmental window remains poorly understood.
Utilizing a highly sensitive and quantitative mass spectrometry approach, we obtain high-quality proteome data spanning seven mouse stages, from full-grown oocyte (FGO) to blastocyst, using 100 oocytes/embryos at each stage. Integrative analyses reveal distinct proteome reprogramming compared to that of the transcriptome or translatome. FGO to 8-cell proteomes are dominated by FGO-stockpiled proteins, while the transcriptome and translatome are more dynamic. FGO-originated proteins frequently persist to blastocyst while corresponding transcripts are already downregulated or decayed. Improved concordance between protein and translation or transcription is observed for genes starting translation upon meiotic resumption, as well as those transcribed and translated only in embryos. Concordance between protein and transcription/translation is also observed for proteins with short half-lives. We built a kinetic model that predicts protein dynamics by incorporating both initial protein abundance in FGOs and translation kinetics across developmental stages.
Through integrative analyses of datasets generated by ultrasensitive methods, our study reveals that the proteome shows distinct dynamics compared to the translatome and transcriptome during mouse OET. We propose that the remarkably stable oocyte-originated proteome may help save resources to accommodate the demanding needs of growing embryos. This study will advance our understanding of mammalian OET and the fundamental principles governing gene expression.
Utilizing a highly sensitive and quantitative mass spectrometry approach, we obtain high-quality proteome data spanning seven mouse stages, from full-grown oocyte (FGO) to blastocyst, using 100 oocytes/embryos at each stage. Integrative analyses reveal distinct proteome reprogramming compared to that of the transcriptome or translatome. FGO to 8-cell proteomes are dominated by FGO-stockpiled proteins, while the transcriptome and translatome are more dynamic. FGO-originated proteins frequently persist to blastocyst while corresponding transcripts are already downregulated or decayed. Improved concordance between protein and translation or transcription is observed for genes starting translation upon meiotic resumption, as well as those transcribed and translated only in embryos. Concordance between protein and transcription/translation is also observed for proteins with short half-lives. We built a kinetic model that predicts protein dynamics by incorporating both initial protein abundance in FGOs and translation kinetics across developmental stages.
Through integrative analyses of datasets generated by ultrasensitive methods, our study reveals that the proteome shows distinct dynamics compared to the translatome and transcriptome during mouse OET. We propose that the remarkably stable oocyte-originated proteome may help save resources to accommodate the demanding needs of growing embryos. This study will advance our understanding of mammalian OET and the fundamental principles governing gene expression.
摘要：
背景：卵母细胞到胚胎的转变（OET）将终末分化的配子转化为全能胚胎，并受到母体mRNA和蛋白质的关键控制，而基因组是沉默的，直到合子基因组激活。转录组，翻译,在这个关键的发育窗口中，蛋白质组的协调仍然知之甚少。
结果：利用高灵敏度和定量的质谱方法，我们获得了跨越七个小鼠阶段的高质量蛋白质组数据，从完整的卵母细胞（FGO）到胚泡，在每个阶段使用100个卵母细胞/胚胎。整合分析揭示了与转录组或翻译组相比不同的蛋白质组重编程。FGO到8细胞蛋白质组由FGO储存的蛋白质主导，而转录组和翻译组更为动态。FGO起源的蛋白质经常持续存在于胚泡中，而相应的转录本已经下调或衰减。对于减数分裂恢复后开始翻译的基因，观察到蛋白质与翻译或转录之间的一致性得到改善。以及仅在胚胎中转录和翻译的那些。对于半衰期短的蛋白质,也观察到蛋白质与转录/翻译之间的一致性。我们建立了一个动力学模型，通过将FGO中的初始蛋白质丰度和跨发育阶段的翻译动力学纳入来预测蛋白质动力学。
结论：通过对超灵敏方法生成的数据集进行综合分析，我们的研究表明，与小鼠OET过程中的翻译组和转录组相比，蛋白质组显示出不同的动力学。我们建议，非常稳定的卵母细胞起源的蛋白质组可能有助于节省资源，以适应生长胚胎的苛刻需求。这项研究将促进我们对哺乳动物OET和控制基因表达的基本原理的理解。
结果：利用高灵敏度和定量的质谱方法，我们获得了跨越七个小鼠阶段的高质量蛋白质组数据，从完整的卵母细胞（FGO）到胚泡，在每个阶段使用100个卵母细胞/胚胎。整合分析揭示了与转录组或翻译组相比不同的蛋白质组重编程。FGO到8细胞蛋白质组由FGO储存的蛋白质主导，而转录组和翻译组更为动态。FGO起源的蛋白质经常持续存在于胚泡中，而相应的转录本已经下调或衰减。对于减数分裂恢复后开始翻译的基因，观察到蛋白质与翻译或转录之间的一致性得到改善。以及仅在胚胎中转录和翻译的那些。对于半衰期短的蛋白质,也观察到蛋白质与转录/翻译之间的一致性。我们建立了一个动力学模型，通过将FGO中的初始蛋白质丰度和跨发育阶段的翻译动力学纳入来预测蛋白质动力学。
结论：通过对超灵敏方法生成的数据集进行综合分析，我们的研究表明，与小鼠OET过程中的翻译组和转录组相比，蛋白质组显示出不同的动力学。我们建议，非常稳定的卵母细胞起源的蛋白质组可能有助于节省资源，以适应生长胚胎的苛刻需求。这项研究将促进我们对哺乳动物OET和控制基因表达的基本原理的理解。
