Fig. 4: Predicted ligand–receptor interactions during EVT invasion.

a, Left, dot plot showing z-score of normalized, log-transformed and variance-scaled gene expression of selected receptors (y-axis) that are upregulated in EVT-1, EVT-2 and/or iEVT (ME3) (x-axis). Right, dot plot showing the presence of selected ligands (y-axis) in cells present in ME3 (invasion front; x-axis). Differential expression as in Extended Data Fig. 8a. Schematic in bottom right represents select ligand–receptor interactions. b, Left, high-resolution multiplexed smFISH of placenta–decidua interface showing HLA-G (EVT) and CD14 (decidual macrophage), and CXCL16 and its cognate receptor CXCR6. Dashed outlines indicate areas shown magnified on the right. Centre, filled and unfilled arrows indicate neighbouring CXCL16-expressing decidual macrophages and CXCR6-expressing EVTs, respectively. Images are representative of two donors. c, Schematic representation of the EVT differentiation experimental design, indicating time points and biological replicates in TSC models (n = 2 donors). d, Dot plot showing normalized, log-transformed and variance-scaled expression of genes (x-axis) that are significantly upregulated (limma, FDR < 0.05, with Bonferroni correction for multiple hypotheses testing) in the EVT subsets upon exposure to CXCL16 compared with control. e, Left, dot plot showing z-score of normalized, log-transformed and variance-scaled gene expression of selected receptors (y-axis) that are upregulated in GC (ME4) (x-axis). Right, dot plot showing the presence (y-axis) of selected ligands in cells present in ME4 (decidual–myometrial border; x-axis). Differential expression as in Extended Data Fig. 8a. Schematic in bottom right represents select ligand–receptor interactions. f, High-resolution multiplexed smFISH of the placenta–decidua interface showing HLA-G and EFNB1, demonstrating that expression of EFNB1 is present throughout EVTs, including iEVTs, and higher in GCs. The inset (bottom centre) illustrates the multinucleated nature of GCs. Images representative of two donors. dM, decidual macrophages; dS, decidual stromal cells; endo-M, maternal endotheial cells; PV, perivascular.