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: 10531091
• 负责人: Mana M Parast
• 金额: $ 167.83万
• 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/10531091
• 关键词: 3-Dimensional; ATAC-seq; Architecture; Atlases; Biological; Biological Assay; Blood; Blood Circulation; Blood specimen; Capillary Endothelial Cell; Cell Nucleus; Cell physiology; Cells; Chromatin; Collaborations; Collection; Communication; Communities; Cytometry; Data; Data Set; Detection; Development; Endocrine; Enrollment; Ensure; Extracellular Matrix; Female; Fetal Growth; Fetus; Foundations; 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; Work; adverse pregnancy outcome; base; 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.

摘要 OSP的目标是生成构建人类三维多尺度地图所需的数据 来自健康的无并发症妊娠的胎盘。OSP1将与OAC和DAC以及其他 HuBMAP中心，以促进在整个联盟内以及与更广泛的科学部门共享数据和资源 社区。胎盘是母亲和胎儿之间的界面，调节营养物质的交换和 代谢废物和产生内分泌信号，促进妊娠和适当的维持 胎儿发育。胎盘主要由胎儿来源的细胞组成，包括基质细胞、毛细血管 内皮细胞和三种类型的滋养细胞：增殖性细胞滋养细胞；激素产生和 转运性合体滋养细胞和侵袭性绒毛外滋养细胞。胎盘中还含有胎儿 和母体免疫细胞，它们介导对感染的免疫反应，并可能在胎盘中发挥作用 发展。胎盘发育和功能的异常与最常见的和 妊娠的严重并发症，但导致不良妊娠结局的机制的细节 仍有待阐明。我们调查团队的优势互补使我们能够获得产前检查 来自相同器官的活体核磁共振和超声成像数据以及分娩后分子图谱数据。 严格的分析前和表征管道将确保收集高质量的生物检验品和 生成可重现的数据。将使用一系列先进的分子图谱技术，包括 大宗和单核转录、染色质可及性和细胞外基质蛋白质组学 高分辨率多路空间转录和成像质量细胞术技术。我们将结合一个 调查方法(我们将从许多受试者的少量样本/切片中收集数据， 这将使我们能够检测与胎儿性别、分娩方式、 或母性因素)使用深度潜水方法(在这种方法中，我们将从许多连续的部分收集数据，从 少量组织块，以构建组织架构的详细模型)。要生成基本的 作为未来旨在确定结构和功能的研究的基础的知识 胎盘功能障碍介导的妊娠并发症的基础扰动，我们提出了两个亚 目标：c.1。从正常足月胎盘、子宫内膜肌层、输卵管生成参考数据集 输卵管和母体血清，以构建这些正常妊娠的3D多尺度地图 并定位胎盘和胎盘之间的细胞外RNA介导的信号转导。 母体组织；以及C.2。要从怀孕期间的胎盘生成参考数据集，请启用 构建人胎盘发育的三维多尺度图，并追踪其分化和 细胞在其中的迁移。