Application of single-cell RNA sequencing in preeclampsia

Preeclampsia (PE) is a pregnancy-specific multisystem disorder and a leading cause of maternal and perinatal morbidity and mortality worldwide. Despite the widely accepted two-stage model involving placental dysfunction and maternal systemic inflammation, the precise cellular and molecular mechanisms underlying its pathogenesis remain incompletely understood. In recent years, single-cell RNA sequencing (scRNA-seq) has emerged as a transformative technology capable of resolving transcriptional heterogeneity at unprecedented resolution, offering new insights into the complex cellular landscape of the maternal-fetal interface. This review systematically summarizes the application of scRNA-seq in advancing the understanding of PE pathogenesis. We first introduce the technical principles and advantages of scRNA-seq over bulk sequencing methods. Subsequently, we highlight key findings from scRNA-seq studies of the normal placenta and decidua, establishing a reference for cellular composition and trophoblast differentiation trajectories. We then focus on studies of PE placentas, which have revealed distinct dysfunction in trophoblast subpopulations-including impaired differentiation, invasion, and accelerated senescence-and have identified novel regulatory molecules such as BHLHE40, NDRG1, and DAB2. Additionally, we discuss scRNA-seq-derived insights into immune dysregulation at the maternal-fetal interface, including altered NK cell subsets, macrophage polarization, and disruption of immune tolerance mediated by molecules such as HLA-F and JUNB. Finally, we explore the translational potential of scRNA-seq in identifying novel biomarkers, constructing predictive models, and enabling disease subtyping for precision medicine. By capturing cell-specific transcriptional changes, scRNA-seq provides a powerful framework for deciphering the complexity of PE and holds promise for improving its prediction, diagnosis, and therapy.