Transcriptomic Profiling of Placental Cells in Preeclampsia as an Effective Tool for Personalized Medicine

Abstract

At present transcriptomics is one of the fastest developing fields of molecular biology, which allows to obtain detailed information about the functional activity of the genome both in normal and pathological conditions. We used modern transcriptomic technologies to comprehensively characterize the whole genome gene expression profile of human placental syncytiotrophoblast cells (STB) in physiological pregnancy and preeclampsia (PE). As a result of our analysis, we identified 26 differentially expressed genes (DEGs) in the STB cells between healthy and diseased states. The cluster of DEGs contains not only well-known candidate genes identified earlier in many foreign whole genome studies of the placenta (for example, LEP, INHBA and FLT1), but also new genes (AC098613.1, AC087857.1, FCRLB, TENM4, PTP4A1P7, LINC01225, etc.) that can be considered as new biological markers of PE and are of interest for further study. Functional enrichment annotation indicated that most of the DEGs were implicated in the signaling pathways of regulation of hormonal secretion, MAPK cascade, ERK1 and ERK2 cascade, positive regulation of cell adhesion and proliferation of endothelial cells. These processes may be associated with the development of PE at the STB cells level. Additionally, we revealed that alternative splicing of the FLT1 gene indicate the important role of this RNA processing mechanism in the pathogenetics of PE due to a significant increase in the transcriptional diversity of genes in STB cells. The expression level of the transcript encoding the protein isoform FLT-1 e15a was significantly increased in patients with PE compared to the control group. This study expands understanding of the molecular mechanisms involved in PE and can serve as a basis for developing of preventive, prognostic and therapeutic strategies in the field of personalized obstetrics.