Single-Cell Transcriptome and RNA Sequencing Reveal Immune-Related Markers of Preeclampsia.

Abstract

Preeclampsia is a leading cause of maternal and fetal mortality, posing a threat to the mother and fetus's lives, but its pathogenesis is not yet clear. This study aimed to find the key target genes regulating preeclampsia in the placental immune microenvironment through single-cell and RNA-sequencing. This study compared the immune microenvironment of the placenta in preeclamptic and non-preeclamptic samples. Gene Ontology Enrichment (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), pseudotime, and cell-cell communication techniques were utilized to analyze the association between immune cell function and the pathogenesis of preeclampsia. Specific transcription factor target genes of immune cells were obtained based on the Scenic package and intersections were taken with their differentially expressed genes (DEGs). Key differential genes analysis was performed on the intersected genes based on the GSE234729 and GSE25906 datasets to obtain differential target genes regulating preeclampsia in immune cells. A total of 10 cell types were annotated in the placenta. Among them, macrophages had the highest immune score, followed by monocytes. GO and KEGG results demonstrated that they might be involved in inflammatory response and vascular remodeling in preeclampsia. Macrophages in the placenta were reclustered and annotated to monocytes, macrophages, and Hofbauer cell subsets, of these, monocytes could differentiate into macrophages and Hofbauer cells. Of all the immune cell-regulated preeclampsia differential genes SLC9A9, SH2B3, SDC3, RCC2, F13A1, CCL2, and CBLB were consistently expressed in two transcriptome datasets, and all were highly expressed in macrophages. These findings suggested that macrophages were implicated in the aberrant immune and inflammatory response of the preeclamptic placenta and found its key target genes that regulate preeclampsia.