Characterization of decidual natural killer cells cell heterogeneity and dynamic evolution in recurrent miscarriage...

This study used scRNA-seq to explore the underlying mechanisms of decidual natural killer cells affecting recurrent miscarriage (RM).

We obtained the GSE214607 scRNA-seq dataset from Gene Expression Omnibus (GEO) database, containing data from 5 normal and 3 RM pregnancy samples. The 'Seurat' and 'Harmony' R package was used for the scRNA-seq analysis. Differentially expressed genes among cell subpopulations were identified using FindAllMarkers function, and the 'Monocle2' package was employed to construct pseudo-time trajectories. Finally, the 'CellChat' package was used to analyze ligand-receptor interactions between cells.

Our analysis revealed altered immune cell composition in RM, with reduced decidual NK (dNK), decidual stromal, and epithelial glandular cells but increased Mono/Macro proportions. Two dNK subclusters were identified: PAEP-high (linked to growth factor signaling) and LGALS1-high (involved in glycolysis and platelet function). Despite similar subcluster frequencies, RM samples showed elevated interferon response genes (e.g. IFITM1, ISG15) and diminished migration/activation signals. Pseudo-time analysis highlighted progressive gene expression changes during RM. CellChat revealed reduced Vascular Endothelial Growth Factor (VEGF) signaling, indicating impaired angiogenesis, and enhanced TNF, MHC-II, and FAS/FASL interactions, suggesting increased inflammation and trophoblast apoptosis. These findings implicate dNK dysfunction in RM and suggest potential therapeutic targets.

Our findings demonstrate dNK cell dysfunction in RM, marked by heightened interferon signaling and aberrant crosstalk with trophoblasts. Integrative analysis of public transcriptomic data suggests that dNK cell-directed interventions represent a putative therapeutic avenue for RM. Insight RM linked to decidual immune imbalance with reduced dNK and increased monocytes/macrophages. Two dNK subclusters (PAEP-high, LGALS1-high) with specific gene expression pattern in RM. RM shows impaired angiogenesis, inflammation, and trophoblast apoptosis in dNK cell-mediated signaling pathways. Dysfunctional dNK cells drive RM, revealing potential therapeutic targets for treatment.