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

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

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). Utilizi...

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Main Authors: Hui-Qi Qu, Kushagra Goel, Kayleigh Ostberg, Diana J. Slater, Fengxiang Wang, James Snyder, Cuiping Hou, Garnet Eister, John J. Connolly, Michael March, Joseph T. Glessner, Charlly Kao, Hakon Hakonarson
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Experimental Biology and Medicine
Subjects:
NK cells
peripheral blood mononuclear cells
single-cell RNA sequencing
single ventricle/hypoplastic left heart syndrome
transcriptome
Online Access:https://www.ebm-journal.org/articles/10.3389/ebm.2025.10524/full
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Summary: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.
ISSN:1535-3699

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