Integration of single-cell sequencing and transcriptomic analysis to identify novel diagnostic biomarkers for...

Pre-eclampsia is a significant obstetric complication. Immune cells within the maternal circulatory system hold substantial promises for the diagnosis and treatment of pre-eclampsia. However, research focusing on the maternal circulatory system remains inadequate.

We conducted differential analysis and weighted correlation network analysis on a dataset to identify blood biomarkers for early-onset pre-eclampsia. These biomarkers were subsequently validated through ELISA. Multiple bioinformatic analyses were subsequently performed to predict the biological functions associated with the selected genes and potential protein‒miRNA regulatory relationships. Additionally, by analysing single-cell transcriptomic data from blood samples, we predicted the genetic profiles of the selected genes, investigated changes in the proportion of blood immune cells and abnormalities in intercellular communication in the pathogenesis of pre-eclampsia, and predicted potential protein-compound interactions.

We identified and validated the expression levels of F2R-like trypsin receptor 1 (F2RL1) and granzyme H (GZMH) in maternal blood samples obtained from women with and without pre-eclampsia. Gene set enrichment analysis revealed that F2RL1 participates in the regulation of classic signaling pathways, including the Toll-like receptor signaling pathway, pattern recognition receptor signaling pathway, oxidative stress-induced endogenous apoptosis signaling pathway, and vesicle targeting process. GZMH primarily contributes to immune processes associated with natural killer cells. Analysis of single-cell sequencing datasets revealed significant alterations in T cells and haematopoietic stem cell growth factor (HSC-G-CSF) within the maternal blood system during the onset of pre-eclampsia. Furthermore, receptor-ligand interaction analysis and protein-compound interaction analysis highlighted the critical role of aspirin in alleviating pre-eclampsia pathology, while also revealing the potential therapeutic value of tyrosine kinase inhibitors.

This study identified the pre-eclampsia biomarkers F2RL1 and GZMH, which showed good diagnostic value. This research provides new insights for the prediction of pre-eclampsia and deepens our understanding of changes in the maternal blood immune system during pre-eclampsia.