Pregnant Female Reproductive Tissue Mapping Center Organ Specific Project

孕妇生殖组织绘图中心器官特定项目

• 批准号: 10670434
• 负责人: Mana M Parast
• 金额: $ 197.89万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10670434
• 关键词: 3-Dimensional; ATAC-seq; Architecture; Atlases; Biological; Biological Assay; Blood; Blood specimen; Capillary Endothelial Cell; Cell Nucleus; Cell physiology; Cells; Chromatin; Circulation; Collaborations; Collection; Communication; Communities; Cytometry; Data; Data Set; Detection; Development; Endocrine; Enrollment; Ensure; Extracellular Matrix; Female; Fetal Growth; Fetus; Functional disorder; Future; Generations; Giant Cells; Goals; Histopathology; Hormones; Human; Human BioMolecular Atlas Program; Image; Immune; Immune response; Immunoassay; In Situ; Infection; Knowledge; Link; Longevity; Magnetic Resonance Imaging; Mammalian Oviducts; Maps; Mediating; Metabolic; Metadata; Molecular; Molecular Analysis; Molecular Profiling; Mothers; Nutrient; Organ; Participant; Performance; Placenta; Placentation; Play; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy Maintenance; Premature Birth; Proteins; Proteomics; RNA; Reproducibility; Resolution; Resource Sharing; Role; Sampling; Signal Pathway; Signal Transduction; Stains; Stromal Cells; Study Subject; Surveys; Syncytiotrophoblast; System; Techniques; Technology; Time; Tissue Model; Tissue Sample; Tissues; Transcript; Ultrasonography; Uterus; Villous; Work; adverse pregnancy outcome; candidate identification; cell motility; cell type; cytotrophoblast; data integration; data sharing; design; digital; extracellular; fetal; fetus cell; healthy pregnancy; human female; imaging study; in vivo; interest; maternal serum; metabolomics; migration; multiple data types; novel; pregnant; prenatal; recruit; reproductive; sex; spatiotemporal; tissue mapping; transcriptome; transcriptome sequencing; transcriptomics; trophoblast; ultrasound; wasting

SUMMARY The goal of the OSP is to generate the data needed to build three-dimensional multiscale maps of the human placenta from healthy uncomplicated pregnancies. OSP1 will interact with the OAC and DAC, as well as other HuBMAP Centers, to facilitate data and resource sharing across the Consortium and with the broader scientific community. The placenta is the interface between mother and fetus, mediating exchange of nutrients and metabolic wastes and producing endocrine signals that promote maintenance of the pregnancy and proper fetal growth. The placenta is comprised largely of cells of fetal origin, including stromal cells, capillary endothelial cells, and three types of trophoblast: proliferative cytotrophoblast; hormone-producing and transport-mediating syncytiotrophoblast; and invasive extravillous trophoblast. The placenta also contains fetal and maternal immune cells, which mediate immunologic responses to infection and may play roles in placental development. Abnormalities in placental development and function have been linked to the most common and serious complications of pregnancy, but details of the mechanisms leading to adverse pregnancy outcomes remain to be elucidated. The complementary strengths of our investigative team enable us to obtain prenatal in vivo MRI and ultrasound imaging data and post-delivery molecular profiling data from the same organs. Rigorous pre-analytical and characterization pipelines will ensure collection of high-quality biospecimens and generation of reproducible data. A range of advanced molecular profiling techniques will be used, including bulk and single-nucleus transcriptomic, chromatin accessibility, and extracellular matrix proteomic profiling, and high-resolution multiplexed spatial transcriptomic and imaging mass cytometry technologies. We will combine a survey approach (in which we will collect data from a small number of samples/sections from many subjects, which will allow us to detect potential differences associated with variables such as fetal sex, mode of delivery, or maternal factors) with a deep dive approach (in which we will collect data from many serial sections from a small number tissue blocks, to build a detailed model of tissue architecture). To generate foundational knowledge to serve as the basis of future studies aimed at identifying the structural and functional perturbations that underlie placental dysfunction-mediated pregnancy complications, we propose two Sub- Aims: C.1. To generate a reference dataset from normal term placentas, uterine endomyometrium, fallopian tubes, and maternal serum, to enable construction of 3D multiscale maps of these normal pregnant reproductive tissues at term, and to map extracellular RNA-mediated signaling between the placenta and maternal tissues; and C.2. To generate a reference dataset from placentas across gestation, to enable construction of 3D multiscale maps of the developing human placenta, and tracking of the differentiation and migration of the cells within it.

概括 OSP的目的是生成建立人类三维多尺度图所需的数据 来自健康的简单怀孕的胎盘。 OSP1将与OAC和DAC以及其他 Hubmap中心，以促进整个财团的数据和资源共享以及更广泛的科学 社区。胎盘是母亲和胎儿之间的界面，介导营养的交换和 代谢废物和产生内分泌信号，可促进怀孕和适当的维持 胎儿生长。胎盘主要由胎儿起源细胞组成，包括基质细胞，毛细血管 内皮细胞和三种类型的滋养细胞：增生性细胞增生型细胞；产生激素和 中断运输的合成细胞塑料；和侵入性的跨性滋养细胞。胎盘还包含胎儿 和母体免疫细胞，介导对感染的免疫反应，并可能在胎盘中起作用 发展。胎盘发育和功能的异常与最常见的相关性 严重的怀孕并发症，但导致不良怀孕结果的机制的细节 仍然有待阐明。我们调查团队的互补优势使我们能够获得产前 体内MRI和超声成像数据以及来自同一器官的分子分子分析数据。 严格的分析前和表征管道将确保收集高质量的生物测量和 生成可再现数据。将使用一系列高级分子分析技术，包括 散装和单核转录组，染色质可及性和细胞外基质蛋白质组学分析，以及 高分辨率多路复用的空间转录组和成像质量细胞仪技术。我们将结合一个 调查方法（在其中我们将从许多受试者的少数样本/部分中收集数据， 这将使我们能够检测到与胎儿性别，分娩方式等变量相关的潜在差异， 采用深度潜水方法（我们将从许多串行部分中收集数据的数据） 少量组织块，以构建组织结构的详细模型）。生成基础 知识成为旨在识别结构和功能的未来研究的基础 胎盘功能障碍介导的妊娠并发症的扰动，我们提出了两个亚 目的：C.1。从正常胎盘，子宫内部肌层，输卵管产生参考数据集 试管和母性血清，以构建这些正常怀孕的3D多尺度地图 术语生殖组织，并绘制胎盘外的细胞外RNA介导的信号传导 母体组织；和C.2。要生成一个从妊娠的胎盘的参考数据集，以启用 建造正在发展的人胎盘的3D多尺度地图，并跟踪分化和 内部细胞的迁移。