The recent advancements of single-cell RNA sequencing in pre-eclampsia.

Preeclampsia (PE) is a multisystem syndrome that manifests after 20 weeks of gestation, with a global incidence of 2%-8%, and is one of the leading causes of maternal and perinatal mortality. Its etiology is complex, involving multiple mechanisms such as abnormal placentation, immune dysregulation, and angiogenic imbalance, with early-onset PE (EOPE) and late-onset PE (LOPE) exhibiting distinct pathological foundations. In recent years, the application of single-cell RNA sequencing (scRNA-seq) has provided a novel perspective for deciphering the cellular heterogeneity and molecular mechanisms of PE. This review systematically summarizes the latest advances in scRNA-seq applications in PE research, focusing on how this technology reveals: (1) Dysfunction of trophoblast subpopulations and its association with defective spiral artery remodeling; (2) Dynamic changes in the immune microenvironment, including macrophage polarization, functional subsets of uNK cells, and T cell regulatory networks; (3) Cell-specific dysregulation of key signaling pathways; (4) The distinct cytopathological features of early-onset versus late-onset PE. Furthermore, scRNA-seq has facilitated the discovery of multi-gene-based early diagnostic models and potential therapeutic targets. Compared to traditional bulk sequencing, scRNA-seq enables the resolution of cellular heterogeneity, identification of rare cell subpopulations, and elucidation of intercellular communication networks. However, its limitations include difficulties in sample acquisition, high technical costs, complex data analysis, and challenges in capturing multinucleated syncytial structures. In the future, scRNA-seq is expected to provide highly promising therapeutic strategies for PE patients.