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谱系分化的启动。这一发育时间框架也具有经济意义，因为大多数辅助生殖技术，如体外胚胎生产，都是在这一时间框架内应用的。我的研究计划将通过研究最近发现的新的转录元件群体做出重大贡献。牛卵母细胞和早期胚胎的转录组学研究表明，这些细胞中含有大量的新型转录本，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仍然是未知的。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。我们的目标是通过根据它们的基因组位置和已知的功能特征对它们进行分类来进一步表征这些新的转录本。它们中的任何一个是否实际上是新的蛋白质编码转录本将被确定。将测量它们在其他组织和早期胚胎发育期间的丰度。将通过确定候选物的细胞定位以及其从细胞中耗尽的生理影响来进行功能评估。为了评估它们是否在基因表达中起作用，它们的表达将与DNA甲基化状态和其他转录物的丰度相关联。这些努力将发展加拿大在研究哺乳动物早期胚胎形成领域的领导地位，但也为将生活条件如孕产妇营养和生殖性能联系起来的新兴领域提供了垫脚石。它还将产生与处理分化细胞的许多关键部门相关的重要知识，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.