The maternal-fetal interface at single-cell resolution: uncovering the cellular anatomy of the placenta and decidua

The maternal-fetal interface represents a critical site of immunological interactions that can greatly influence pregnancy outcomes. The unique cellular composition and cell-cell interactions taking place within these tissues has spurred substantial research efforts focused on the maternal-fetal interface. With the recent advent of single-cell technologies, multiple investigators have applied such methods to gain an unprecedented level of insight into maternal-fetal communication. Here, we provide an overview of the dynamic cellular composition and cell-cell communications at the maternal-fetal interface as reported by single-cell investigations. By primarily focusing on data from pregnancies in the second and third trimesters, we aim to showcase how single-cell technologies have bolstered the foundational understanding of each cell's contribution to physiologic gestation. Indeed, single-cell technologies have enabled the examination of classical placental cells, such as the trophoblast, as well as uncovered new roles for structural cells now recognized as active participants in pregnancy and parturition, such as decidual and fetal stromal cells, which are reviewed herein. Furthermore, single-cell data investigating the ontogeny, function, differentiation, and interactions among immune cells present at the maternal-fetal interface, namely macrophages, T cells, dendritic cells, neutrophils, mast cells, innate lymphoid cells, natural killer cells, and B cells are discussed in this review. Moreover, a key output of single-cell investigations is the inference of cell-cell interactions, which has been leveraged to not only dissect the intercellular communications within specific tissues but also between compartments such as the decidua basalis and placental villi. Collectively, this review emphasizes the ways by which single-cell technologies have expanded the understanding of cell composition and cellular processes underlying pregnancy in mid-to-late gestation at the maternal-fetal interface, which can prompt their continued application to reveal new pathways and targets for the treatment of obstetrical disease.