3D Multiscale Spatial Mapping of the Human Placenta

摘要 OSP1 的目标是生成健康人胎盘的三维多尺度图。 无并发症的妊娠。 OSP1 将与其他 FR TMC 核心/项目和其他 HuBMAP 交互 促进整个联盟以及更广泛的科学领域的数据和资源共享的中心 社区。胎盘是母亲和胎儿之间的界面，介导营养物质和胎儿的交换。 代谢废物并产生内分泌信号，促进怀孕和正常的维持 胎儿生长。胎盘主要由胎儿来源的细胞组成，包括基质细胞、毛细血管细胞 内皮细胞和三种类型的滋养层：增殖性细胞滋养层；产生激素和 运输介导的合体滋养层；和侵袭性绒毛外滋养层。胎盘中还含有胎儿 和母体免疫细胞，介导对感染的免疫反应，并可能在胎盘中发挥作用 发展。胎盘发育和功能异常与最常见和最常见的疾病有关 严重妊娠并发症，但导致不良妊娠结局的机制细节 仍有待阐明。为了使未来的研究能够确定结构和功能 胎盘功能障碍介导的妊娠并发症背后的扰动，我们建议产生一个 正常足月胎盘的参考数据集。重要的是，我们的调查能力具有互补性 团队使我们能够获得纵向产前体内 MRI 和超声成像数据以及产后数据 来自同一器官的生物力学和分子分析数据。严格的预分析和表征 管道将确保收集高质量的生物样本并生成可重复的数据。一系列 将使用先进的分子分析技术，包括初始批量和解离的单细胞 转录组学、染色质可及性和细胞外基质蛋白质组学分析以鉴定组成细胞 类型并优先考虑目标。然后将使用高分辨率多路复用空间来询问这些目标 转录组学和成像质谱流式技术。由此产生的数据，链接到综合 元数据将持续传输至 DAC，并与 DAC 协作进行分析，以及 HIVE 的调查员。最后，我们将生成可探索的胎盘 3D 多尺度图 获得对不同细胞类型之间、细胞之间的物理和调节关系的新见解 及其环境，以及微观水平上的组织结构和整个器官功能之间的关系。

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.