Embryonal non-coding RNAs in the human placenta and the maternal circulation.

人类胎盘和母体循环中的胚胎非编码 RNA。

• 批准号: 315156279
• 负责人: Professor Dr. Udo Markert
• 金额: --
• 依托单位: Klinik für Geburtsmedizin
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/315156279?language=en
• 关键词: Embryonal; non; coding; RNAs; human

Non-coding RNAs (ncRNAs) play a central and regulatory role in almost all cells, organs, and species which has been broadly recognized since the human ENCODE project and several other genome projects. Nevertheless, we know only a small fraction of ncRNAs. Moreover, long non-coding RNAs are known only for about five years and have been very marginally investigated in the placenta. To date, most examples of ncRNAs which have been identified to be specific for fetal tissues, such as placenta, are members of the group of microRNAs (miRNAs). It can be expected that the fairly larger group of other ncRNA exerts much more powerful influences and effects. Thus, we see the need to expand the knowledge about ncRNAs in the placenta and ncRNAs released from it.Inside the placenta, the fetal syncytiotrophoblast forms the interface between fetus and mother, from which exosomes and microvesicles are permanently released into the maternal circulation. These particles contain fetal proteins and RNA for communication with neighboring and distant maternal cells. The number, size and content of particles may reflect or predict placental disorders and can be assessed in maternal serum samples. As many of the known trophoblast-specific miRNAs are human-primate-specific it may be expected that also other, currently unknown ncRNAs are species-restricted and can, therefore, only be investigated in human placentae. Several severe pregnancy pathologies, including preeclampsia, are human-specific and their pathomechanisms are not yet understood. We expect that the knowledge on novel placental ncRNA will have the potential of revolutionizing the understanding of regulation processes inside the placenta and of fetal-maternal communication.In this proposed project, we aim to answer the following questions:(1) Which (partially newly characterized) ncRNAs are fetus specific?(2) Which of these fetally expressed ncRNAs are derived from trophoblast cells? Which trophoblast-derived ncRNAs reach maternal blood packed within (3) microvesicles or (4) exosomes? Furthermore, we aim to identify highly abundant ncRNAs via PCR from maternal serum. This may contribute to identification of disease associated marker genes in subsequent projects. Finally, we plan to determine differences between natural trophoblast ncRNAs and ncRNAs in commonly used cell lines (JEG-3 choriocarcinoma cells and HTR8/SVneo immortalized first trimester trophoblast cells). Subsequently, both cell lines will be used for silencing and overexpression of trophoblast specific ncRNA for identification of their targets and basic functions.

非编码RNA（Non-coding RNA，ncRNA）在几乎所有的细胞、器官和物种中都发挥着重要的调控作用，自人类ENCODE计划和其他几个基因组计划以来，ncRNA已被广泛认识。然而，我们只知道一小部分的ncRNA。此外，长链非编码RNA仅在大约五年前被发现，并且在胎盘中的研究非常有限。迄今为止，已被鉴定为对胎儿组织如胎盘具有特异性的ncRNA的大多数实例是microRNA（miRNA）组的成员。可以预期，其他ncRNA的相当大的群体发挥更强大的影响和作用。因此，我们认为有必要扩大有关胎盘中ncRNA及其释放的ncRNA的知识。在胎盘内部，胎儿合胞滋养层形成胎儿和母亲之间的界面，外泌体和微泡从该界面永久释放到母体循环中。这些颗粒含有胎儿蛋白和RNA，用于与邻近和遥远的母体细胞进行通信。颗粒的数量、大小和含量可以反映或预测胎盘疾病，并且可以在母体血清样品中进行评估。由于许多已知的滋养层特异性miRNA是人灵长类特异性的，因此可以预期其他目前未知的ncRNA也是物种限制的，因此只能在人胎盘中研究。几种严重的妊娠病理，包括先兆子痫，是人类特有的，其病理机制尚未了解。我们期望新的胎盘ncRNA的知识将有可能彻底改变胎盘内的调节过程和胎儿-母体communication.In这个拟议的项目，我们的目标是回答以下问题：（1）哪些（部分新的特点）ncRNA是胎儿特异性的？(2)哪些胎儿表达的ncRNA来自滋养层细胞？哪些滋养层来源的ncRNA到达（3）微泡或（4）外泌体中的母体血液？此外，我们的目标是通过PCR从母体血清中鉴定高度丰富的ncRNA。这可能有助于在后续项目中识别疾病相关的标记基因。最后，我们计划确定天然滋养层ncRNA和常用细胞系（JEG-3绒毛膜癌细胞和HTR 8/SVneo永生化早孕滋养层细胞）中ncRNA之间的差异。随后，两种细胞系将用于滋养层特异性ncRNA的沉默和过表达，以鉴定其靶标和基本功能。