Small RNAs at the placental maternal communication interface

胎盘母体通讯接口处的小RNA

• 批准号: 8411118
• 负责人: Yoel Sadovsky
• 金额: $ 22.31万
• 依托单位: MAGEE-WOMEN'S RES INST AND FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-01-16 至 2014-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8411118
• 关键词: Address; Adult; Affect; Allografting; Biological Markers; Blood; Blood Circulation; Blood Platelets; Cells; Clinical; Communication; Computational Biology; DNA Methylation; Data; Development; Developmental Process; Dimensions; Disease; Embryo; Embryonic Development; Endothelial Cells; Epigenetic Process; Fetal Growth; Fetal Growth Retardation; Fetus; Functional RNA; Functional disorder; Future; Gene Expression; Generations; Genetic Transcription; Glean; Goals; Growth; Health; Human; Hypoxia; Injury; Knowledge; Light; Link; Maternal-Fetal Exchange; Messenger RNA; Metabolic syndrome; MicroRNAs; Mothers; Nature; Newborn Infant; Organism; Pathologic Processes; Pathology; Pathway interactions; Pattern; Physiological Processes; Placenta; Placentation; Plasma; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Premature Birth; Proteins; RNA; RNA Databases; RNA Interference; Regulation; Reproducibility; Research; Risk; Role; Science; Signal Transduction; Small Nuclear RNA; Small RNA; Techniques; Technology; Testing; Tissues; Woman; clinically relevant; computerized tools; deep sequencing; design; epigenomics; fetal; histone modification; improved; in vivo; injured; mRNA Expression; nanoparticle; next generation; novel; peripheral blood; protein expression; research study; stem; stillbirth; trafficking; trophoblast

DESCRIPTION (provided by applicant): Our long-term research goal is to improve pregnancy outcome and newborn health by supporting each fetus in attaining its innate growth potential. In this exploratory proposal, we deploy a novel research plan that centers on epigenomic signals that control placenta-maternal communication. We posit that microRNA and other small RNA signals have an extraordinary significance in regulation of placental and maternal gene expression and consequently, successful pregnancy. Unlike changes in DNA methylation, histone modifications or nucleosomal remodeling, miRNAs and other small RNAs directly modulate the expression of mRNAs and proteins. While prevalent in every tissue and capable of modulating diverse developmental, physiological and pathological processes, the function of most miRNA remains unknown. The placenta distinctively interfaces between the semi-allograft fetus and the maternal host. Importantly, the human placenta expresses unique miRNA species that are not normally present elsewhere. We have assembled a trans-disciplinary team that spans expertise in development, computational biology, and pathology, sharing the common goal of elucidating the role of microRNAs and small RNAs in the cross talk between the mother and the feto-placental unit. Having already defined differential microRNA expression and their unique function in primary human trophoblasts in normal and hypoxic conditions, we now seek to use next generation deep sequencing technology to comprehensively interrogate microRNA and small RNA species in the human maternal blood and the placenta, and deploy novel computational tools to analyze dynamic changes in microRNA and small RNA expression in normal pregnancies or pregnancies complicated by clinically relevant placental injury. We will specifically assess the nature of small RNAs assembled in vesicular nano-particles (exosomes), which may traffic small RNAs between the mother and the feto-placental unit. Information gleaned from our data may not only illuminate non-coding RNA pathways that influence human embryonic development, but may also suggest new, clinically-relevant signals, designed to inform the risk of placental injury and sub-standard pregnancy outcome.

描述(申请人提供)：我们的长期研究目标是通过支持每个胎儿实现其固有的生长潜力来改善妊娠结局和新生儿健康。在这个探索性的提案中，我们部署了一个新的研究计划，以控制胎盘-母体沟通的表观基因组信号为中心。我们认为，microRNA和其他小RNA信号在调节胎盘和母体基因表达方面具有非凡的意义，因此，成功怀孕。与DNA甲基化、组蛋白修饰或核小体重塑的变化不同，miRNAs和其他小RNA直接调节mRNAs和蛋白质的表达。虽然miRNA广泛存在于所有组织中，并能够调节不同的发育、生理和病理过程，但大多数miRNA的功能仍不清楚。胎盘在半同种异体胎儿和母体宿主之间有明显的界面。重要的是，人类胎盘表达了其他地方通常不存在的独特的miRNA物种。我们已经组建了一个跨学科的团队，他们拥有发育、计算生物学和病理学方面的专业知识，共同的目标是阐明microRNAs和Small RNAs在母亲和胎儿-胎盘单位之间的交叉对话中的作用。在已经确定了正常和低氧条件下原代人类滋养层细胞中microRNA的差异表达及其独特的功能后，我们现在寻求使用下一代深度测序技术来全面询问人类母体血液和胎盘中的microRNA和小RNA物种，并部署新的计算工具来分析正常妊娠或合并临床相关胎盘损伤的妊娠中microRNA和小RNA表达的动态变化。我们将具体评估组装在泡状纳米颗粒(外体)中的小RNA的性质，这可能会在母亲和胎儿-胎盘单位之间运输小RNA。从我们的数据中收集的信息不仅可能阐明影响人类胚胎发育的非编码RNA途径，还可能提出新的临床相关信号，旨在告知胎盘损伤和不合标准的妊娠结局的风险。