Cellular commitment to mortality: mouse early embryo

细胞对死亡的承诺：小鼠早期胚胎

• 批准号: 7194072
• 负责人: Minoru S Ko
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7194072
• 关键词: RNA; binding proteins; developmental genetics; early embryonic stage; egg /ovum; embryogenic cleavage; embryonic stem cell; gene expression; gene expression profiling; laboratory mouse; mammalian embryology; microarray technology; protein structure

We concentrate on the critical distinction between immortal early embryonic cells and mortal differentiating derivative cells. We apply large-scale systematic methodology "embryogenomics" to the study of preimplantation development - the process of fertilized egg gradually losing its totipotency. In our previous work, we have completed the microarray-based global expression profiling of all preimplantation stages in mouse, which revealed and characterized the distinctive patterns of maternal RNA degradation and two major transient waves of de novo transcription. The first wave corresponds to zygotic genome activation (ZGA); the second wave, named mid-preimplantation gene activation (MGA), precedes the dynamic morphological and functional changes from the morula to blastocyst stage. We propose a cascade of gene activation from maternal RNA/protein sets to ZGA gene sets and thence to MGA gene sets ("waves of gene activation hypothesis"). Among the candidate genes identified in this study, we have selected and studied one novel gene encoding a zinc finger binding protein, which shows a transient expression in 2-cell embryos. The functional analysis of this gene, including a gene disruption study, is underway.

我们专注于永生早期胚胎细胞和致死分化衍生细胞之间的关键区别。我们应用大规模的系统方法论“胚胎基因组学”来研究着床前发育--受精卵逐渐失去全能性的过程。在我们之前的工作中，我们已经完成了基于微阵列的小鼠着床前所有阶段的全局表达谱，揭示并表征了母体RNA降解的独特模式和从头转录的两个主要瞬时波。第一波对应于合子基因组激活(ZGA)，第二波称为着床前中期基因激活(MGA)，先于桑拿期到囊胚期的形态和功能的动态变化。我们提出了一个从母体RNA/蛋白质组到ZGA基因组再到MGA基因组的基因激活级联(“基因激活波假说”)。在本研究确定的候选基因中，我们选择并研究了一个新的编码锌指结合蛋白的基因，该基因在2-细胞胚胎中瞬时表达。该基因的功能分析，包括基因中断研究，正在进行中。