Placentomics using a novel method to isolate circulating placental derivatives

项目摘要 胎盘在确保发育中的胎儿获得足够的营养、保护和支持方面起着至关重要的作用。 胎儿，对长期健康有重要影响。曾经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，也许是为了促进胎儿-母亲 通过细胞、细胞外囊泡、DNA和RNA的直接相互作用和交换进行通信。的 因此，转移到母体循环中的胎盘物质的数量和类型提供了了解 胎盘本身的功能。本建议的总体目标是系统地评价 胎盘滋养层细胞和胎盘来源的细胞外囊泡的转录组和表观基因组， 妊娠期间的母体循环，利用一种新的高通量方法分离胎盘 材料我们将汇集一个跨学科的团队，在生物工程，产科和 生殖科学，基因组科学和基因组生物统计学，研究一个精心定义的队列， 参加全球预防早产和死产联盟生物储存库的妇女。 此外，患有先兆子痫（胎盘功能障碍的主要表现）的妇女将作为 对照人群。从这些主题中，我们将评估核酸，细胞外 囊泡和妊娠期间从胎儿转移到母亲的滋养层细胞。具体来说，我们将 分离的循环滋养层细胞（使用集合决策等分排列，eDAR）和合体滋养层细胞- 衍生的细胞外囊泡（使用温度响应富集模块，TREM）从母体 怀孕期间的循环胎盘来源物质的转录组学和表观基因组学分析 建立有关妊娠期间胎盘组学的基础信息，并为未来的研究提供信息。

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.