Discovering molecular signatures in kidney transplant biopsies with borderline changes and isolated V-lesions: single-cell RNA-sequencing analysis of human blood and tissue Spatial transcriptomics
Abstract Acute T cell-mediated rejection (TCMR) is one of the most important causes of kidney graft injury and loss; however, in-depth transcriptomic analyses of relevant tissues and circulating immune cells are limited. In this study, we conducted single-cell RNA sequencing (scRNA-seq) on periphera...
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Nature Portfolio
2025-07-01
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| Online Access: | https://doi.org/10.1038/s41598-025-05191-x |
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| author | Jeongin Song Minji Kang Yunyoung Jang Christine Suh-Yun Joh Ha Yeon Shin Julia Young Baik Hyun Seung Choi Kyu Hong Kim Seong Min Lee Seung-Min Cha Hyunah Ku Ahram Han Sang Il Min Jongwon Ha Kyung Chul Moon Sehoon Park Seung Seok Han Hajeong Lee Dong Ki Kim Kook Hwan Oh Kwon Wook Joo Ji Hwan Moon Chung-Gyu Park Yon Su Kim Seung Hee Yang Hyun Je Kim Yong Chul Kim |
| author_facet | Jeongin Song Minji Kang Yunyoung Jang Christine Suh-Yun Joh Ha Yeon Shin Julia Young Baik Hyun Seung Choi Kyu Hong Kim Seong Min Lee Seung-Min Cha Hyunah Ku Ahram Han Sang Il Min Jongwon Ha Kyung Chul Moon Sehoon Park Seung Seok Han Hajeong Lee Dong Ki Kim Kook Hwan Oh Kwon Wook Joo Ji Hwan Moon Chung-Gyu Park Yon Su Kim Seung Hee Yang Hyun Je Kim Yong Chul Kim |
| author_sort | Jeongin Song |
| collection | DOAJ |
| description | Abstract Acute T cell-mediated rejection (TCMR) is one of the most important causes of kidney graft injury and loss; however, in-depth transcriptomic analyses of relevant tissues and circulating immune cells are limited. In this study, we conducted single-cell RNA sequencing (scRNA-seq) on peripheral blood mononuclear cells and spatial transcriptomics using kidney allograft biopsy samples. The scRNA-seq study included four patients with borderline rejection or biopsy-proven TCMR and two with no evidence of TCMR. For spatial analysis, we compared tissue specimens from one patient diagnosed with borderline rejection and another patient with TCMR to their time-zero protocol biopsies. Six regions of interest per biopsy section were selected, focusing on the evident T-cell infiltration area in the tubulointerstitium and glomeruli. Integrating two methodologies, we pinpointed CD8+ effector memory T cell (TEM) expression profiles and key upregulated genes, including LTB, GZMK, PSME2, UBE2L6, and STAT1. Among them, STAT1 was confirmed as a hub gene through network and pathway analysis. Immunohistochemistry and immunofluorescence on kidney allograft tissue validated the co-expression of STAT1 with CD8, indicating an active inflammatory response. Our findings suggest the presence of a CD8+ STAT1+ TEM subset with features of clonal expansion, providing additional insight into the immunological processes associated with TCMR. |
| format | Article |
| id | doaj-art-506d4c893a534c59b698bfb8b5cf726a |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-506d4c893a534c59b698bfb8b5cf726a2025-08-20T03:38:12ZengNature PortfolioScientific Reports2045-23222025-07-0115111810.1038/s41598-025-05191-xDiscovering molecular signatures in kidney transplant biopsies with borderline changes and isolated V-lesions: single-cell RNA-sequencing analysis of human blood and tissue Spatial transcriptomicsJeongin Song0Minji Kang1Yunyoung Jang2Christine Suh-Yun Joh3Ha Yeon Shin4Julia Young Baik5Hyun Seung Choi6Kyu Hong Kim7Seong Min Lee8Seung-Min Cha9Hyunah Ku10Ahram Han11Sang Il Min12Jongwon Ha13Kyung Chul Moon14Sehoon Park15Seung Seok Han16Hajeong Lee17Dong Ki Kim18Kook Hwan Oh19Kwon Wook Joo20Ji Hwan Moon21Chung-Gyu Park22Yon Su Kim23Seung Hee Yang24Hyun Je Kim25Yong Chul Kim26Department of Internal Medicine, Dongguk University Ilsan HospitalDepartment of Biomedical Sciences, Seoul National University Graduate SchoolDepartment of Internal Medicine, Seoul National University HospitalDepartment of Biomedical Sciences, Seoul National University Graduate SchoolDepartment of Biomedical Sciences, Seoul National University Graduate SchoolDepartment of Biomedical Sciences, Seoul National University Graduate SchoolDepartment of Biomedical Sciences, Seoul National University Graduate SchoolDepartment of Biomedical Sciences, Seoul National University Graduate SchoolDepartment of Biomedical Sciences, Seoul National University Graduate SchoolDepartment of Biomedical Sciences, Seoul National University Graduate SchoolDepartment of Biomedical Sciences, Seoul National University Graduate SchoolDepartment of Surgery, Seoul National University HospitalDepartment of Surgery, Seoul National University HospitalDepartment of Surgery, Seoul National University HospitalDepartment of Pathology, Seoul National University HospitalDepartment of Internal Medicine, Seoul National University HospitalDepartment of Internal Medicine, Seoul National University HospitalDepartment of Internal Medicine, Seoul National University HospitalDepartment of Internal Medicine, Seoul National University HospitalDepartment of Internal Medicine, Seoul National University HospitalDepartment of Internal Medicine, Seoul National University HospitalSamsung Genome Institute, Samsung Medical CenterDepartment of Biomedical Sciences, Seoul National University Graduate SchoolDepartment of Internal Medicine, Seoul National University HospitalKidney Research Institute, Seoul National University Medical Research CenterDepartment of Biomedical Sciences, Seoul National University Graduate SchoolDepartment of Internal Medicine, Seoul National University HospitalAbstract Acute T cell-mediated rejection (TCMR) is one of the most important causes of kidney graft injury and loss; however, in-depth transcriptomic analyses of relevant tissues and circulating immune cells are limited. In this study, we conducted single-cell RNA sequencing (scRNA-seq) on peripheral blood mononuclear cells and spatial transcriptomics using kidney allograft biopsy samples. The scRNA-seq study included four patients with borderline rejection or biopsy-proven TCMR and two with no evidence of TCMR. For spatial analysis, we compared tissue specimens from one patient diagnosed with borderline rejection and another patient with TCMR to their time-zero protocol biopsies. Six regions of interest per biopsy section were selected, focusing on the evident T-cell infiltration area in the tubulointerstitium and glomeruli. Integrating two methodologies, we pinpointed CD8+ effector memory T cell (TEM) expression profiles and key upregulated genes, including LTB, GZMK, PSME2, UBE2L6, and STAT1. Among them, STAT1 was confirmed as a hub gene through network and pathway analysis. Immunohistochemistry and immunofluorescence on kidney allograft tissue validated the co-expression of STAT1 with CD8, indicating an active inflammatory response. Our findings suggest the presence of a CD8+ STAT1+ TEM subset with features of clonal expansion, providing additional insight into the immunological processes associated with TCMR.https://doi.org/10.1038/s41598-025-05191-xKidney transplantation/NephrologyKidney allograft function/DysfunctionRejectionT cell mediated rejectionBorderline changeTranslational research/Science |
| spellingShingle | Jeongin Song Minji Kang Yunyoung Jang Christine Suh-Yun Joh Ha Yeon Shin Julia Young Baik Hyun Seung Choi Kyu Hong Kim Seong Min Lee Seung-Min Cha Hyunah Ku Ahram Han Sang Il Min Jongwon Ha Kyung Chul Moon Sehoon Park Seung Seok Han Hajeong Lee Dong Ki Kim Kook Hwan Oh Kwon Wook Joo Ji Hwan Moon Chung-Gyu Park Yon Su Kim Seung Hee Yang Hyun Je Kim Yong Chul Kim Discovering molecular signatures in kidney transplant biopsies with borderline changes and isolated V-lesions: single-cell RNA-sequencing analysis of human blood and tissue Spatial transcriptomics Scientific Reports Kidney transplantation/Nephrology Kidney allograft function/Dysfunction Rejection T cell mediated rejection Borderline change Translational research/Science |
| title | Discovering molecular signatures in kidney transplant biopsies with borderline changes and isolated V-lesions: single-cell RNA-sequencing analysis of human blood and tissue Spatial transcriptomics |
| title_full | Discovering molecular signatures in kidney transplant biopsies with borderline changes and isolated V-lesions: single-cell RNA-sequencing analysis of human blood and tissue Spatial transcriptomics |
| title_fullStr | Discovering molecular signatures in kidney transplant biopsies with borderline changes and isolated V-lesions: single-cell RNA-sequencing analysis of human blood and tissue Spatial transcriptomics |
| title_full_unstemmed | Discovering molecular signatures in kidney transplant biopsies with borderline changes and isolated V-lesions: single-cell RNA-sequencing analysis of human blood and tissue Spatial transcriptomics |
| title_short | Discovering molecular signatures in kidney transplant biopsies with borderline changes and isolated V-lesions: single-cell RNA-sequencing analysis of human blood and tissue Spatial transcriptomics |
| title_sort | discovering molecular signatures in kidney transplant biopsies with borderline changes and isolated v lesions single cell rna sequencing analysis of human blood and tissue spatial transcriptomics |
| topic | Kidney transplantation/Nephrology Kidney allograft function/Dysfunction Rejection T cell mediated rejection Borderline change Translational research/Science |
| url | https://doi.org/10.1038/s41598-025-05191-x |
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