Cellular commitment to mortality: analyses of mouse earl

细胞对死亡率的承诺：小鼠早期的分析

• 批准号: 7325191
• 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/7325191
• 关键词: Cellular; commitment; mortality; analyses; mouse

Preimplantation development encompasses the period from fertilization to implantation. These early embryos are the source of Embryonic stem (ES) cells and the locus of nuclear reprogramming. Therefore, the molecular study of these early embryos is very important for stem cell biology and its potential therapeutic applications to aging and dysfunctional organs/tissues. Our goal is to apply systematic genomic approaches to these early embryos and to understand their regulation of gene expression. We carried out DNA 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: zygotic genome activation (ZGA) and mid-preimplantation gene activation (MGA). Through these analyses, we identified a number of genes that show unique expression patterns. We have demonstrated that one of them, named Zga1, is expressed exclusively in 2-cell mouse embryos and ES cells and plays a critical role in the progression of preimplantation development. We also found that a gene called Chuk shows constant RNA levels throughout preimplantation development and can be used as an internal standard suitable for quantitative RT-PCR (Falco et al., 2006). We also developed a technique to do large-scale Whole Mount In Situ Hybridization (WISH), which allows us to reveal the spatial expression patterns of 91 genes in mouse preimplantation embryos (Yoshikawa et al., 2006). We are currently studying the functions of these genes in details.

着床前发育包括从受精到着床的时期。这些早期胚胎是胚胎干细胞（ES）的来源和核重编程的位点。因此，这些早期胚胎的分子研究对于干细胞生物学及其在衰老和功能失调器官/组织的潜在治疗应用具有重要意义。我们的目标是应用系统的基因组方法来研究这些早期胚胎，并了解它们对基因表达的调控。我们对小鼠着床前的所有阶段进行了基于DNA微阵列的全球表达谱分析，揭示并表征了母体RNA降解的独特模式和两个主要的新生转录瞬态波：合子基因组激活（ZGA）和着床前中期基因激活（MGA）。通过这些分析，我们发现了一些表现出独特表达模式的基因。我们已经证明其中一种名为Zga1的基因仅在2细胞小鼠胚胎和胚胎干细胞中表达，并在胚胎着床前发育过程中发挥关键作用。我们还发现一个名为Chuk的基因在植入前发育过程中显示出恒定的RNA水平，可以用作适用于定量RT-PCR的内部标准（Falco等，2006）。我们还开发了一种大规模全Mount原位杂交（WISH）技术，该技术使我们能够揭示小鼠着床前胚胎中91个基因的空间表达模式（Yoshikawa et al., 2006）。我们目前正在详细研究这些基因的功能。