3D Multiscale Spatial Mapping of the Human Placenta

摘要 OSP1的目标是从健康的人胎盘中生成三维多尺度地图 不复杂的怀孕。OSP1将与其他FR TMC核心/项目和其他HuBMAP交互 中心，以促进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。以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的基础扰动，我们建议产生一个 正常足月胎盘的参考数据集。重要的是，我们调查的优势互补 团队使我们能够获得纵向产前活体MRI和超声成像数据以及分娩后 来自相同器官的生物力学和分子图谱数据。严谨的预分析和表征 管道将确保收集高质量的生物标本并产生可复制的数据。一系列 将使用先进的分子图谱技术，包括初始批量和分离的单细胞 转录、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 确定目标的类型和优先顺序。然后将使用高分辨率多路复用空间来询问这些目标 转录学和成像质量细胞术技术。产生的数据，链接到全面的 元数据，将在持续的基础上转移到发援会，并与发援会协作进行分析，以及 蜂巢里的调查人员。最后，我们将生成可供探索的胎盘的3D多比例地图 对不同类型的细胞之间、细胞之间的物理和调控关系有新的见解 以及微观水平上的组织结构与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.