Single cell quantification of translation control in early mouse development

小鼠早期发育中翻译控制的单细胞定量

• 批准号: 10711352
• 负责人: Can Cenik
• 金额: $ 38.92万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10711352
• 关键词: Address; Alleles; Cells; Congenital Abnormality; Development; Embryo; Embryonic Development; Gene Expression; Genetic Transcription; Genome; Measurement; Messenger RNA; Methods; Mus; Nucleotides; Pre-implantation Embryo Development; Process; Productivity; Protein Biosynthesis; Proteins; Proteome; Research; Resolution; Ribosomes; Shapes; Technology; Translational Repression; Translations; blastocyst; innovation; insight; mouse development; posttranscriptional; preimplantation; prevent; programs; ribosome profiling; transcriptome; vertebrate embryos

The initial stages of vertebrate embryo development proceed in the absence of transcription. Consequently, protein abundance of preimplantation embryos is regulated by post-transcriptional gene expression programs. In particular, new protein synthesis is required for productive embryogenesis as inhibition of translation prevents activation of the zygotic genome and leads to arrested development. Despite this critical function, translational dynamics in single mammalian embryos have remained unexplored due to technological limitations. To address this critical gap and technological need, we propose to comprehensively and quantitatively determine the dynamics of translational control during early mouse development at single nucleotide and single embryo resolution. The proposed research will apply a transformative technology that my lab developed enabling the measurement of translation in single preimplantation embryos. In this study, we will determine allele-specific ribosome engagement of mRNAs and characterize the underlying mechanisms. The proposed study will be significant as it will be the first transcriptome-wide characterization of translational control in preimplantation mammalian development at single embryo resolution and will reveal how the early embryo executes specific gene expression programs to shape its proteome.

在没有转录的情况下，脊椎动物胚胎发育的初始阶段进行。 因此，植入前胚胎的蛋白质丰度受到转录后的调节 基因表达程序。特别是，生产性需要新的蛋白质合成 胚胎发生为抑制翻译可防止粘染性基因组的激活，并导致 被捕的发展。尽管功能如此关键功能，但单哺乳动物中的转化动力学 由于技术局限性，胚胎仍未探索。解决这个关键差距 技术需求，我们建议全面和定量确定的动态 小鼠在单核苷酸和单个胚胎的早期发育过程中的翻译控制 解决。拟议的研究将应用我的实验室开发的变革性技术 能够在单个植入前胚胎中测量翻译。在这项研究中，我们将 确定特定于等位基因的mRNA核糖体参与并表征基础 机制。拟议的研究将是重要的，因为它将是第一个全转录组的 植入前哺乳动物发育中翻译控制的表征 分辨率并将揭示早期胚胎如何执行特定的基因表达程序以形成 它的蛋白质组。