3D Multiscale Spatial Mapping of the Human Placenta

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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.