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.

The authors have declared no competing interest.

The study was supported by the Institutional Development Funds from the Children's Hospital of Philadelphia to the Center for Applied Genomics, and The Children's Hospital of Philadelphia Endowed Chair in Genomic Research to HH.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

This study received approval from the Institutional Review Board at the Children's Hospital of Philadelphia.

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All data produced in the present study are available upon reasonable request to the corresponding author.