Single-Cell Analysis of Preeclamptic Cord Blood Mononuclear Cells Revealed Activation of Heme-Associated Signalling...

Preeclampsia is a severe gestational complication whose molecular pathogenesis remains poorly understood despite extensive research. It is now recognized that both maternal and fetal cells contribute to disease progression. Notably, single-cell RNA sequencing of cord blood cells from preeclamptic pregnancies has not been previously investigated, and this became the focus of our study. In this work, we performed flow cytometry, single-cell RNA sequencing and bioinformatics analysis of cord blood mononuclear cells from preeclampsia and control groups. Bulk RNA-sequencing data of preeclamptic cord blood from open source was also analysed. We observed a significant decrease in the expression of the CD3, CD8 and CD4 markers in cord blood mononuclear cells in the preeclampsia group. Single-cell RNA sequencing revealed activation of iron- and heme-associated signalling pathways in various cell types (nonclassical monocytes, naive СD4⁺ and CD8⁺ T cells, T-helpers 2, NK cells and naive СD4⁺ regulatory T cells) in cord blood during preeclampsia. Analysis of open-source bulk RNA-sequencing data confirmed our findings of activation of heme-related signalling pathways in preeclamptic cord blood samples. These results may suggest the activation of compensatory mechanisms, potentially mediated by the proangiogenic heme degradation products carbon monoxide and biliverdin. Additionally, free heme may act as a proinflammatory damage-associated molecular pattern in preeclampsia. Further studies are needed to elucidate the direct relationship between these mechanisms and placental heme metabolism.