Cellular commitment to mortality: analyses of mouse early embryo

细胞对死亡的承诺：小鼠早期胚胎的分析

• 批准号: 8148279
• 负责人: Minoru Ko
• 金额: $ 54.14万
• 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/8148279
• 关键词: Embryo; Mus; mortality

We carried out DNA microarray-based global expression profiling of all preimplantation stages in mouse. It 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). 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. Through these analyses, we identified a number of genes that show unique expression patterns. We have demonstrated that one of them, named Zscan4, is expressed exclusively in 2-cell mouse embryos and ES cells and plays a critical role in the progression of preimplantation development. We also identified genes, named Trim43a, Trim43b, and Trim43c, whose expression began at the 2-cell stage, peaked at the 8-cell/morula stage, and dramatically fell by the blastocyst stage. We are currently investigating whether Zscan4 overexpression can increase the potency of ES cells by injecting Zscan4-manipulated ES cells into mouse blastocysts.

我们对小鼠所有植入前阶段进行了基于 DNA 微阵列的全局表达谱分析。它揭示并表征了母体 RNA 降解的独特模式和从头转录的两个主要瞬时波：合子基因组激活 (ZGA) 和中期植入前基因激活 (MGA)。我们还开发了一种进行大规模整体原位杂交 (WISH) 的技术，使我们能够揭示小鼠植入前胚胎中 91 个基因的空间表达模式。通过这些分析，我们确定了许多显示独特表达模式的基因。我们已经证明其中一种名为 Zscan4 的蛋白仅在 2 细胞小鼠胚胎和 ES 细胞中表达，并且在植入前发育过程中发挥着关键作用。我们还鉴定了名为 Trim43a、Trim43b 和 Trim43c 的基因，其表达在 2 细胞阶段开始，在 8 细胞/桑葚胚阶段达到顶峰，并在囊胚阶段急剧下降。我们目前正在研究 Zscan4 过表达是否可以通过将 Zscan4 操作的 ES 细胞注射到小鼠囊胚中来增加 ES 细胞的效力。