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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Frontiers Media S.A.
2025-08-01
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| Series: | Experimental Biology and Medicine |
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| Online Access: | https://www.ebm-journal.org/articles/10.3389/ebm.2025.10524/full |
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| author | 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 Joseph T. Glessner Joseph T. Glessner Charlly Kao Hakon Hakonarson Hakon Hakonarson Hakon Hakonarson Hakon Hakonarson Hakon Hakonarson |
| author_facet | 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 Joseph T. Glessner Joseph T. Glessner Charlly Kao Hakon Hakonarson Hakon Hakonarson Hakon Hakonarson Hakon Hakonarson Hakon Hakonarson |
| author_sort | Hui-Qi Qu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-22b80a70fda54164bde8a679a5670dbe |
| institution | Kabale University |
| issn | 1535-3699 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Experimental Biology and Medicine |
| spelling | doaj-art-22b80a70fda54164bde8a679a5670dbe2025-08-20T03:36:41ZengFrontiers Media S.A.Experimental Biology and Medicine1535-36992025-08-0125010.3389/ebm.2025.1052410524Natural killer cell subpopulations in the peripheral blood of single ventricle/hypoplastic left heart syndrome patients via single-cell RNA sequencingHui-Qi Qu0Kushagra Goel1Kayleigh Ostberg2Diana J. Slater3Fengxiang Wang4James Snyder5Cuiping Hou6Garnet Eister7John J. Connolly8Michael March9Joseph T. Glessner10Joseph T. Glessner11Joseph T. Glessner12Charlly Kao13Hakon Hakonarson14Hakon Hakonarson15Hakon Hakonarson16Hakon Hakonarson17Hakon Hakonarson18The Center for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesThe Center for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesThe Center for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesThe Center for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesThe Center for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesThe Center for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesThe Center for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesThe Center for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesThe Center for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesThe Center for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesThe Center for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesDepartment of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United StatesDivision of Human Genetics, Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesThe Center for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesThe Center for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesDepartment of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United StatesDivision of Human Genetics, Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesDivision of Pulmonary Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesFaculty of Medicine, University of Iceland, Reykjavik, IcelandNatural 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.https://www.ebm-journal.org/articles/10.3389/ebm.2025.10524/fullNK cellsperipheral blood mononuclear cellssingle-cell RNA sequencingsingle ventricle/hypoplastic left heart syndrometranscriptome |
| spellingShingle | 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 Joseph T. Glessner Joseph T. Glessner Charlly Kao Hakon Hakonarson Hakon Hakonarson Hakon Hakonarson Hakon Hakonarson Hakon Hakonarson Natural killer cell subpopulations in the peripheral blood of single ventricle/hypoplastic left heart syndrome patients via single-cell RNA sequencing Experimental Biology and Medicine NK cells peripheral blood mononuclear cells single-cell RNA sequencing single ventricle/hypoplastic left heart syndrome transcriptome |
| title | Natural killer cell subpopulations in the peripheral blood of single ventricle/hypoplastic left heart syndrome patients via single-cell RNA sequencing |
| title_full | Natural killer cell subpopulations in the peripheral blood of single ventricle/hypoplastic left heart syndrome patients via single-cell RNA sequencing |
| title_fullStr | Natural killer cell subpopulations in the peripheral blood of single ventricle/hypoplastic left heart syndrome patients via single-cell RNA sequencing |
| title_full_unstemmed | Natural killer cell subpopulations in the peripheral blood of single ventricle/hypoplastic left heart syndrome patients via single-cell RNA sequencing |
| title_short | Natural killer cell subpopulations in the peripheral blood of single ventricle/hypoplastic left heart syndrome patients via single-cell RNA sequencing |
| title_sort | natural killer cell subpopulations in the peripheral blood of single ventricle hypoplastic left heart syndrome patients via single cell rna sequencing |
| topic | NK cells peripheral blood mononuclear cells single-cell RNA sequencing single ventricle/hypoplastic left heart syndrome transcriptome |
| url | https://www.ebm-journal.org/articles/10.3389/ebm.2025.10524/full |
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