Spatial single-cell analysis identifies placental villi structural and immune remodeling across gestation

Pregnancies rely upon the balance between fetal and maternal immune systems. Employing imaging mass cytometry, this study creates a spatial map landscape to unravel the cellular dynamics within the placental villi (PV). Consistent with previous data we report structural remodeling in PV, highlighted by increased syncytial trophoblasts, vascular smooth muscle cells, and endothelial cells in term PV. Additionally, we identified that rare immune populations including dendritic cells, innate lymphoid cells, and myeloid-derived suppressor cells in mid-gestation were more abundant and activated than in term placentas, suggesting a potentially tolerogenic state. Conversely, various macrophage subtypes were increased and in combination with rare T-cells exhibited heightened activation markers, possibly indicating increased signaling in preparation for parturition. In mid-gestation, fibroblasts had increased interactions with trophoblasts, while term samples exhibited close adjacencies between trophoblasts, vascular smooth muscle cells, and macrophages. This study offers insights into the PV cellular composition changes between mid and full-term samples, providing a foundation for future studies to understand the mechanisms of preterm birth and other pregnancy complications.