Placentomics using a novel method to isolate circulating placental derivatives

使用新方法分离循环胎盘衍生物的胎盘组学

• 批准号: 9356571
• 负责人: Daniel T Chiu
• 金额: $ 62.94万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-20 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9356571
• 关键词: Aliquot; Apoptosis; Biomedical Engineering; Biometry; Blood; Blood Circulation; Cells; Characteristics; Clinical; Code; Communication; Computer Analysis; DNA; DNA Fragmentation; Data; Detection; Discipline of obstetrics; Disease; Enrollment; Ensure; Epigenetic Process; Evaluation; Evolution; Fetus; Foundations; Functional disorder; Future; Genome; Genomics; Genotype; Goals; Health; Hypoxia; Invaded; Magnetism; Maternal-Fetal Exchange; Measurement; Methodology; Methods; Modality; Mothers; Nature; Normal Range; Nucleic Acids; Nucleosomes; Output; Pattern; Periodicity; Placenta; Play; Population; Pre-Eclampsia; Pregnancy; Pregnancy Complications; RNA; Reperfusion Therapy; Role; Sampling; Science; Severity of illness; Sex Characteristics; Spiral Artery of the Endometrium; Syncytiotrophoblast; System; Temperature; Time; Transport Vesicles; Untranslated RNA; Woman; base; biobank; cell free DNA; cohort; cytotrophoblast; epigenome; epigenomics; extracellular vesicles; fetal; indexing; new technology; novel; novel strategies; premature; prevent; reproductive; stillbirth; transcriptome; transcriptome sequencing; transcriptomics; trophoblast

PROJECT SUMMARY The placenta plays crucial roles in ensuring adequate nourishment, protection, and support of the developing fetus, with important ramifications for long-term health. Once thought to be a perfect barrier between fetus and mother, the placenta is now understood to be involved in and perhaps to facilitate fetal-maternal communication through direct interaction and exchange of cells, extracellular vesicles, DNA and RNA. The quantity and type of placental material transferred to maternal circulation thus provides a window into the function of the placenta itself. The overarching goal of this proposal is to systematically evaluate the transcriptome and the epigenome of trophoblast cells and placental-derived extracellular vesicles in the maternal circulation during pregnancy, harnessing a novel, high-throughput approach for isolation of placental material. We will bring together an interdisciplinary team with expertise in bioengineering, obstetrics and reproductive sciences, genome sciences, and genomic biostatistics to study a meticulously defined cohort of women enrolled in the biorepository of the Global Alliance to Prevent Prematurity and Stillbirth (GAPPS). Additionally, women with preeclampsia, a major manifestation of placental dysfunction, will serve as a comparator population. From these subjects, we will evaluate characteristics of nucleic acids, extracellular vesicles, and trophoblast cells transferred from the fetus to the mother during pregnancy. Specifically, we will isolate circulating trophoblast cells (using ensemble-decision aliquot ranking, eDAR) and syncytiotrophoblast- derived extracellular vesicles (using temperature-responsive enrichment module, TREM) from maternal circulation during pregnancy. Transcriptomic and epigenomic analysis of placental-derived material will establish foundational information about placentomics during pregnancy and inform future studies.

项目总结 胎盘在确保足够的营养、保护和支持发育中起着至关重要的作用。 胎儿，对长期健康有重要影响。一度被认为是胎儿和胎儿之间的完美屏障 母亲，胎盘现在被理解为参与并可能促进胎儿-母体 通过细胞、胞外小泡、DNA和RNA的直接相互作用和交换进行通信。这个 因此，转移到母体循环的胎盘物质的数量和类型提供了一个了解 胎盘本身的功能。这项提案的总体目标是系统地评估 胎盘滋养层细胞和细胞外小泡的转录组和表观基因组 孕期母体循环，利用一种新的高通量方法分离胎盘 材料。我们将汇聚一支具有生物工程、产科和医疗专业知识的跨学科团队 生殖科学、基因组科学和基因组生物统计学，以研究一组精心定义的 妇女加入了全球预防早产和死产联盟(GAPPS)的生物库。 此外，患有先兆子痫的妇女，胎盘功能障碍的主要表现，将作为 比较器数量。从这些科目中，我们将评估细胞外核酸的特征 囊泡和滋养层细胞在怀孕期间从胎儿转移到母亲。具体来说，我们将 分离循环滋养层细胞(使用整体决策等分等级，EDAR)和合体滋养层细胞 来自母体的细胞外小泡(使用温度响应型浓缩模块，TREM) 怀孕期间的血液循环。胎盘来源物质Will的转录和表观基因组分析 建立怀孕期间胎盘组学的基础信息，并为未来的研究提供信息。