Characterizing preeclamptic developmental lung injury pathways through human placental spatial transcriptomics

Bronchopulmonary dysplasia (BPD) continues to impact the health of preterm infants worldwide. Preeclampsia (PE), a placental-driven pregnancy disorder, has a strong clinical association with BPD risk. We hypothesize that preeclampsia causes a unique type of developmental lung injury that predisposes infants to an increased risk of BPD. Research on human placental tissues is needed to more clearly define the role of PE in developmental lung injury. A new approach to human placental analysis is spatial transcriptomics (Sp-Tr), a technique which produces spatially oriented gene expression data from cells in their native tissue environment. Overall design: Placental tissues were collected from pregnant patients with severe PE or gestational hypertension (GHTN). Samples were matched for mode of delivery and infant gender. Tissues were evaluated using the 10x Genomics Visium Sp-Tr platform. Data were analyzed using the Seurat spatial workflow. The counts were normalized using SCTransform, dimensionality reduction and clustering were performed using RunPCA, FindNeighbors, FindClusters, and RunUMAP functions. Clusters corresponding with cellular niches were annotated using the FindMarkers function to identify placental cell-specific phenotype markers followed by analysis of differential gene expression comparing PE vs GHTN.