3D Multiscale Spatial Mapping of the Human Placenta

人类胎盘 3D 多尺度空间测绘

基本信息

批准号：
10119158
负责人：
Mana M Parast
金额：
$ 32.62万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-25 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10119158
关键词：
3-Dimensional ATAC-seq Area Biological Markers Biomechanics Blood Body mass index Capillary Endothelial Cell Cell Differentiation process Cells Cellular Structures Chromatin Chromosome Mapping Clinical Clinical Data Collection Communities Cytometry Data Data Set Development Diagnosis Distal Endocrine Endothelium Enrollment Ensure Environment Ethnic group Evaluation Extracellular Matrix Female Fetal Growth Fetus Functional disorder Future Gene Expression Generations Goals Histopathology Hormones Human Human BioMolecular Atlas Program Image Immune Immune response Immune system Infection Lesion Link Magnetic Resonance Imaging Maps Mass Spectrum Analysis Maternal Age Measurement Mediating Metabolic Metadata Microscopic Modality Molecular Molecular Profiling Mothers Nutrient Organ Outcome Pathologic Perfusion Perfusion Weighted MRI Placenta Placental Hormones Placentation Play Pregnancy Pregnancy Complications Pregnancy Maintenance Pregnancy Outcome Proteins Proteomics Reproducibility Research Personnel Resolution Resource Sharing Role Sampling Signal Transduction Stromal Cells Structure Surface Syncytiotrophoblast System Techniques Technology Tissues Ultrasonography Villous Work adverse pregnancy outcome arteriole base biobank biomarker panel cell type cohort cytotrophoblast data management data sharing design early pregnancy fetal fetus cell immunoregulation in vivo in vivo imaging insight macrophage male molecular marker new technology novel novel strategies pregnant prenatal protein expression racial and ethnic recruit reproductive response single-cell RNA sequencing stem cell proliferation transcriptomics trophoblast wasting

项目摘要

SUMMARY The goal of OSP1 is to generate three-dimensional multiscale maps of the human placenta from healthy uncomplicated pregnancies. OSP1 will interact with the other FR TMC Cores/Projects and the 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. To enable future studies aimed at identifying the structural and functional perturbations that underlie placental dysfunction-mediated pregnancy complications, we propose to generate a reference dataset from normal term placentas. Importantly, the complementary strengths of our investigative team enable us to obtain longitudinal prenatal in vivo MRI and ultrasound imaging data and post-delivery biomechanical and 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 initial bulk and dissociated single-cell transcriptomic, chromatin accessibility, and extracellular matrix proteomic profiling to identify component cell types and prioritize targets. These targets will then be interrogated using high-resolution multiplexed spatial transcriptomic and imaging mass cytometry technologies. The resulting data, linked to comprehensive metadata, will be transferred on an ongoing basis to the DAC, and analyzed collaboratively with the DAC, and investigators at the HIVE. Finally, we will to generate 3D multiscale maps of the placenta that can be explored to gain novel insights into the physical and regulatory relationships among different cell types, between cells and their environment, and between tissue structure on the microscopic level and whole-organ function.

概括 OSP1的目的是从健康中生成人体胎盘的三维多尺度图简单的怀孕。 OSP1将与其他FR TMC核心/项目和其他Hubmap互动中心促进整个财团以及更广泛的科学的数据和资源共享社区。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。为了使未来的研究旨在识别结构和功能胎盘功能障碍介导的妊娠并发症的扰动，我们建议生成一个来自正常术语胎盘的参考数据集。重要的是，我们调查的互补优势团队使我们能够在体内MRI和超声成像数据和交付后获得纵向产前来自同一器官的生物力学和分子分析数据。严格的分析和特征管道将确保收集高质量的生物测量和生成可再现数据。范围将使用高级分子分析技术，包括初始散装和解散的单细胞转录组，染色质可及性和细胞外基质蛋白质组学分析以识别组件细胞类型和优先级目标。然后，这些目标将使用高分辨率多路复用空间来审问转录组和成像质量细胞仪技术。由此产生的数据，链接到综合元数据将持续转移到DAC，并与DAC合作，并且蜂巢的调查人员。最后，我们将生成可以探索的胎盘的3D多尺度地图为了获得对不同细胞类型之间物理和调节关系的新见解，细胞之间及其环境，以及微观水平的组织结构和全器官功能。