AUTHOR=Qu Hui-Qi , Goel Kushagra , Ostberg Kayleigh , Slater Diana J. , Wang Fengxiang , Snyder James , Hou Cuiping , Eister Garnet , Connolly John J. , March Michael , Glessner Joseph T. , Kao Charlly , Hakonarson Hakon 

TITLE=Natural killer cell subpopulations in the peripheral blood of single ventricle/hypoplastic left heart syndrome patients via single-cell RNA sequencing

JOURNAL=Experimental Biology and Medicine

VOLUME=Volume 250 - 2025

YEAR=2025

URL=https://www.ebm-journal.org/journals/experimental-biology-and-medicine/articles/10.3389/ebm.2025.10524

DOI=10.3389/ebm.2025.10524

ISSN=1535-3699

ABSTRACT=Natural Killer (NK) cells are integral components of the innate immune system, recognizing and eliminating virus-infected cells. They may play a crucial role in the immune response and contribute to the complications associated with Single Ventricle/Hypoplastic Left Heart Syndrome (SV/HLHS). Utilizing single-cell RNA sequencing (scRNA-seq), NK cells from peripheral blood mononuclear cells (PBMCs) were analyzed in three de-identified SV/HLHS cases and three healthy controls. This study identified two novel NK cell subpopulations that could not be detected by conventional scRNA-seq pipelines or traditional flow cytometry. These subpopulations exhibit distinct gene expression profiles linked to the heterogeneity of immune responsiveness and stress adaptation in NK cells. In SV/HLHS patients, one cluster showed a significant upregulation of androgen response and downregulation of heme metabolism compared to healthy controls. Our study offers new insights into the fine-tuning of immune modulation that could help mitigate complications in SV/HLHS. It suggests that while NK cells in SV/HLHS adapt to support survival in a challenging physiological environment, these adaptations may compromise their ability to effectively respond to additional stresses, such as infections and inflammation.