Characterization of Natural Killer Cell Subpopulations in the Blood of Single Ventricle/Hypoplastic Left Heart Syndrome Patients Using Single-Cell RNA Sequencing

We utilized single-cell RNA sequencing (scRNA-seq) to examine peripheral blood mononuclear cells (PBMCs) from patients with Single Ventricle/Hypoplastic Left Heart Syndrome (SV/HLHS), and demonstrated a more pronounced correlation between gene expression in Natural Killer (NK) cells and SV/HLHS compared to other PBMC cell types. Our scRNA-seq analysis of NK cells in this study identified two distinct clusters with gene expression patterns linked to immune responsiveness and adaptation to stress. While this finding underscores the heterogeneity of NK cells, it provides new insights into fine-tuning of immune modulation that could prevent complications in SV/HLHS. Specifically, our study suggests that while NK cells in SV/HLHS are adapting to support survival in a challenging physiological environment, these adaptations may compromise their ability to manage additional stresses such as infections and inflammation.