Studying the emerging contributions of long non-coding RNAs as drivers of early embryogenesis.

哺乳动物生命的第一周涉及一系列关键事件，包括发育能力卵母细胞的形成、受精、胚胎基因组激活和细胞系分化的开始。这一发展时限也具有财政意义，因为大多数辅助生殖技术，如体外胚胎生产，都在这一时限内应用。迄今为止，我们对胚胎发生的机制知之甚少。我的研究计划将通过研究最近发现的一个新的转录元素种群而做出重大贡献。牛卵母细胞和早期胚胎的转录组学研究表明，这些细胞含有大量的新转录物，其中许多是长链非编码rna。研究还表明，这种RNA群体受到环境压力的深刻影响。它们对胚胎发生的贡献大部分仍然未知。据推测，它们在胚胎发生过程中起着关键作用，是基因表达调控和细胞分化的重要因素。目标是通过根据基因组位置和已知功能特征对它们进行分类，进一步表征这些新的转录本。它们中是否有新的蛋白质编码转录本将被确定。它们在其他组织和早期胚胎发育期间的丰度将被测量。功能评估将通过确定候选人的细胞定位以及他们从细胞中消耗的生理影响来进行。为了评估它们是否在基因表达中发挥作用，它们的表达将与DNA甲基化状态和其他转录物的丰度平行。这些努力将使加拿大在哺乳动物早期胚胎制造研究领域发挥领导作用，同时也为将产妇营养和生殖性能等生活条件联系起来的新兴领域提供跳板。它还将产生与许多关键领域有关的重要知识，这些领域涉及分化细胞，如癌症、干细胞和再生研究。

The first week of mammalian life involves a succession of key events that include the formation of a developmentally competent oocyte, fertilization, embryonic genome activation and initiation of cell lineage differentiation. This developmental time frame is also of financial significance since most assisted reproductive technologies, such as in vitro embryo production, are applied within it. To date, very little is known about the mechanisms driving embryogenesis. My research program will significantly contribute by studying a new population of transcribed elements that was recently discovered. Transcriptomic surveys of bovine oocytes and early embryos indicate that these cells harbor a large contingent of novel transcripts, many of them being long non-coding RNAs. It was also shown that this RNA population is profoundly influenced by environmental stresses. Their contribution to embryogenesis is still mostly unknown. It is hypothesized that they play a pivotal role during embryogenesis and are important factors in gene expression regulation and cellular differentiation. The objectives are to further characterize these novel transcripts by sorting them according to their genomic location and known functional features. Whether any of them are actually novel protein encoding transcripts will be determined. Their abundance in other tissues and during early embryo development will be measured. Functional assessments will be conducted by determining the cellular localization of candidates as well as the physiological impacts of their depletion from the cells. To assess whether they play a role in gene expression, their expression will be paralleled with the state of DNA methylation and abundance of other transcripts. These efforts will develop Canadian leadership in the field studying the making of a mammalian early embryo but also provide a stepping stone to the emerging field linking living conditions such as maternal nutrition and reproductive performances. It will also generate important knowledge relevant to many key sectors dealing with differentiating cells such as cancer, stem cells and regenerative research.