Project description:HCA Placental Infection Atlas
Self-renewing human trophoblast stem cells (hTSC) can give rise to major trophoblast lineages, including syncytiotrophoblast (SCT) and extravillous trophoblast (EVT). hTSC has facilitated the study of placental development and function in vitro. Here, we aim to utilise the hTSC line (HMDMC 20/0005) to study human placental infection and inflammation. This study will provide the opportunity to better understand the pathogenesis of human placenta in the event of infection and inflammation. In brief, differentiated hTSC will be infected with relevant pathogens and stimulated with a panel of inflammatory cytokines. We will use single-cell genomic and spatial approaches to characterise cellular heterogeneity in response to infection or cytokines stimulus. In parallel, we will investigate the interaction between iPSC-derived macrophages with different trophoblast lineages during the course of infection using single-cell genomic and spatial methods.
This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/
Project description:Trophoblast organoids (TOs) hold great promise for elucidating human placental development and function. By deriving TOs in on-going pregnancies using chorionic villus sampling (CVS), we established a platform to study trophoblast differentiation and function in early pregnancy, including pregnancies with different fetal genetic abnormalities. We addressed cellular heterogeneity of CVS-derived TOs by providing a single-cell transcriptomic atlas and show that CVS-TOs recapitulate key aspects of the human placenta, including syncytial fusion and hormone synthesis. This study demonstrates the utility of trophoblast organoids for investigating genetic defects in the placenta and describes an experimental platform for future personalized placental medicine approaches, including genotype-phenotype mapping.
Project description:The placenta is a complex organ with multiple immune and non-immune cell types that promotes fetal tolerance and facilitates nutrient and oxygen transfer. Diverse placental structures have evolved to accomplish the singular goal of protecting and nourishing the fetus. The nonhuman primate placenta is the most similar to the human placenta, but the extent to which single cell populations recapitulate those in the human is unknown. As the nonhuman primate is a key experimental model of pregnancy complications, it is essential to understand the degree of similarity in single-cell populations across the maternal-fetal interface. We constructed a single-cell atlas of the placenta from the pigtail macaque in the third trimester, comprised of three different tissues at the maternal-fetal interface: the chorionic villi, chorioamniotic membranes, and the maternal decidua. Each tissue was separately dissociated into single cells and processed through the 10X Genomics single-cell RNA-Seq (scRNA-Seq) pipeline. Samples were aggregated, filtered, and analyzed using Seurat. We performed unsupervised clustering followed by cluster annotation. Additional analyses included determining the maternal-fetal origins of cell populations, scRNA velocity, gene ontology enrichment, and cell-cell communication. The single-cell populations in the pigtail macaque were strikingly similar in their identity and relative frequency to that observed in humans. The third trimester pigtail macaque single-cell atlas enables the identification of cellular sub-clusters that are analogous to the human and provides a powerful resource for understanding the impact of infectious disease and other experimental perturbations on the nonhuman primate placenta.
Project description:The human placenta is a dynamic and cellular heterogeneous organ, which is critical in fetomaternal homeostasis and the development of preeclampsia. Previous work has shown that placenta-derived cell-free RNA increases during pregnancy. We applied large-scale microfluidic single-cell transcriptomic technology to comprehensively characterize cellular heterogeneity of the human placentas and identified multiple placental cell-type–specific gene signatures. Analysis of the cellular signature expression in maternal plasma enabled noninvasive delineation of the cellular dynamics of the placenta during pregnancy and the elucidation of extravillous trophoblastic dysfunction in early preeclampsia.