A Single-Cell Transcriptomic Atlas of the Pigtail Macaque Placenta in Late Gestation

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. Ten pregnant pigtail macaques either received (1) choriodecidual and intra-amniotic saline infusions after surgical implantation of choriodecidual and amniotic catheters (n=5) or (2) five subcutaneous inoculations of media along the forearm (n=5). The gestational age at tissue collection spanned the late second and third trimester (118-150 days gestation; term gestation = 172 days).