The mechanism underlying B-cell developmental dysfunction in Kawasaki disease based on single-cell transcriptomic sequencing
BackgroundKawasaki disease (KD) is an acute systemic vasculitis that can lead to acquired heart disease in children mostly from in developed countries. The previous research showed that B cells in KD patients underwent a profound change in both the cell numbers and types after intravenous immunoglob...
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Frontiers Media S.A.
2024-10-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1438640/full |
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| author | Qiuping Lin Zhen Wang Guohui Ding Guang Li Liqin Chen Qingzhu Qiu Sirui Song Wei Liu Xunwei Jiang Min Huang Min Huang Libing Shen Tingting Xiao Lijian Xie Lijian Xie Lijian Xie |
| author_facet | Qiuping Lin Zhen Wang Guohui Ding Guang Li Liqin Chen Qingzhu Qiu Sirui Song Wei Liu Xunwei Jiang Min Huang Min Huang Libing Shen Tingting Xiao Lijian Xie Lijian Xie Lijian Xie |
| author_sort | Qiuping Lin |
| collection | DOAJ |
| description | BackgroundKawasaki disease (KD) is an acute systemic vasculitis that can lead to acquired heart disease in children mostly from in developed countries. The previous research showed that B cells in KD patients underwent a profound change in both the cell numbers and types after intravenous immunoglobulin (IVIG) therapy.MethodsWe performed the single-cell RNA-sequencing for the peripheral blood mononuclear cells (PBMCs) from three febrile patients and three KD patients to investigate the possible mechanism underlying B cell developmental dysfunction in KD. The pseudo-time analysis was employed to study the developmental trajectories of the PBMCs in febrile control and KD patients.ResultsOverall single-cell expression profiles show that the biological processes of immunity, B cell activation pathway and their related biological entities are repressed in KD patients before IVIG treatment compared to febrile patient and KD patients after IVIG treatment. The differentially expressed gene analyses further demonstrate that B cell signaling pathway is downregulated in B cells and plasma blast cells of KD patients before treatment while cell cycle genes and MYC gene are upregulated in dendritic cells (DCs) and hematopoietic stem and progenitor cells (HSPCs) of KD patients before treatment. The biological process of immune response is upregulated in the HSPCs of KD patients before treatment in our dataset while the biological process of inflammatory response is upregulated in the HSPCs of KD patients before treatment in GSE168732 dataset. Single-cell trajectory analyses demonstrate that KD patients before treatment have a shortened developmental path in which B cells and T cells are failed to differentiate into separate lineages. HSPD1 and HSPE1 genes show an elevated expression level in the early cell development stage of KD patients before treatment accompanied with the repression of MYC, SPI1, MT2A and UBE2C genes. Our analyses of all B cells from KD patients before treatment show most of B cells are arrested in a transitional state with an ill developmental path compared with febrile patients and KD patients after treatment.ConclusionOur results indicate that the immune premature HSPCs accompanied with the abnormal expression dynamics of cell cycle and SPI1 genes are the mechanism underlying B cell developmental dysfunction in KD patients. |
| format | Article |
| id | doaj-art-449d2e10c8e04339925874fe4f33cd98 |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2024-10-01 |
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| series | Frontiers in Immunology |
| spelling | doaj-art-449d2e10c8e04339925874fe4f33cd982025-08-20T02:09:47ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-10-011510.3389/fimmu.2024.14386401438640The mechanism underlying B-cell developmental dysfunction in Kawasaki disease based on single-cell transcriptomic sequencingQiuping Lin0Zhen Wang1Guohui Ding2Guang Li3Liqin Chen4Qingzhu Qiu5Sirui Song6Wei Liu7Xunwei Jiang8Min Huang9Min Huang10Libing Shen11Tingting Xiao12Lijian Xie13Lijian Xie14Lijian Xie15Department of Cardiology, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, ChinaInstitute for Digital Health, International Human Phenome Institutes (Shanghai), Shanghai, ChinaDaozhi Precision Medicine Technology Co., LTD, Shanghai, ChinaDepartment of Cardiology, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Cardiology, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Cardiology, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Cardiology, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Cardiology, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Cardiology, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaInstitute of Pediatric Infection, Immunity, and Critical Care Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaInstitute for Digital Health, International Human Phenome Institutes (Shanghai), Shanghai, ChinaDepartment of Cardiology, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Cardiology, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaInstitute of Pediatric Infection, Immunity, and Critical Care Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Pediatrics, Jinshan Hospital, Fudan University, Shanghai, ChinaBackgroundKawasaki disease (KD) is an acute systemic vasculitis that can lead to acquired heart disease in children mostly from in developed countries. The previous research showed that B cells in KD patients underwent a profound change in both the cell numbers and types after intravenous immunoglobulin (IVIG) therapy.MethodsWe performed the single-cell RNA-sequencing for the peripheral blood mononuclear cells (PBMCs) from three febrile patients and three KD patients to investigate the possible mechanism underlying B cell developmental dysfunction in KD. The pseudo-time analysis was employed to study the developmental trajectories of the PBMCs in febrile control and KD patients.ResultsOverall single-cell expression profiles show that the biological processes of immunity, B cell activation pathway and their related biological entities are repressed in KD patients before IVIG treatment compared to febrile patient and KD patients after IVIG treatment. The differentially expressed gene analyses further demonstrate that B cell signaling pathway is downregulated in B cells and plasma blast cells of KD patients before treatment while cell cycle genes and MYC gene are upregulated in dendritic cells (DCs) and hematopoietic stem and progenitor cells (HSPCs) of KD patients before treatment. The biological process of immune response is upregulated in the HSPCs of KD patients before treatment in our dataset while the biological process of inflammatory response is upregulated in the HSPCs of KD patients before treatment in GSE168732 dataset. Single-cell trajectory analyses demonstrate that KD patients before treatment have a shortened developmental path in which B cells and T cells are failed to differentiate into separate lineages. HSPD1 and HSPE1 genes show an elevated expression level in the early cell development stage of KD patients before treatment accompanied with the repression of MYC, SPI1, MT2A and UBE2C genes. Our analyses of all B cells from KD patients before treatment show most of B cells are arrested in a transitional state with an ill developmental path compared with febrile patients and KD patients after treatment.ConclusionOur results indicate that the immune premature HSPCs accompanied with the abnormal expression dynamics of cell cycle and SPI1 genes are the mechanism underlying B cell developmental dysfunction in KD patients.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1438640/fullKawasaki diseasesingle-cell transcriptomic sequencingB cell developmental dysfunctionHSPD1HSPE1MYC |
| spellingShingle | Qiuping Lin Zhen Wang Guohui Ding Guang Li Liqin Chen Qingzhu Qiu Sirui Song Wei Liu Xunwei Jiang Min Huang Min Huang Libing Shen Tingting Xiao Lijian Xie Lijian Xie Lijian Xie The mechanism underlying B-cell developmental dysfunction in Kawasaki disease based on single-cell transcriptomic sequencing Frontiers in Immunology Kawasaki disease single-cell transcriptomic sequencing B cell developmental dysfunction HSPD1 HSPE1 MYC |
| title | The mechanism underlying B-cell developmental dysfunction in Kawasaki disease based on single-cell transcriptomic sequencing |
| title_full | The mechanism underlying B-cell developmental dysfunction in Kawasaki disease based on single-cell transcriptomic sequencing |
| title_fullStr | The mechanism underlying B-cell developmental dysfunction in Kawasaki disease based on single-cell transcriptomic sequencing |
| title_full_unstemmed | The mechanism underlying B-cell developmental dysfunction in Kawasaki disease based on single-cell transcriptomic sequencing |
| title_short | The mechanism underlying B-cell developmental dysfunction in Kawasaki disease based on single-cell transcriptomic sequencing |
| title_sort | mechanism underlying b cell developmental dysfunction in kawasaki disease based on single cell transcriptomic sequencing |
| topic | Kawasaki disease single-cell transcriptomic sequencing B cell developmental dysfunction HSPD1 HSPE1 MYC |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1438640/full |
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