Immune landscape in rejection of renal transplantation revealed by high-throughput single-cell RNA sequencing
Background: The role of the cellular level in kidney transplant rejection is unclear, and single-cell RNA sequencing (scRNA-seq) can reveal the single-cell landscape behind rejection of human kidney allografts at the single-cell level.Methods: High-quality transcriptomes were generated from scRNA-se...
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| Format: | Article |
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Frontiers Media S.A.
2023-07-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2023.1208566/full |
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| author | Ning Wen Ning Wen Ning Wen Jihua Wu Jihua Wu Jihua Wu Haibin Li Haibin Li Haibin Li Jixiang Liao Liugen Lan Xiawei Yang Guangyi Zhu Zhiying Lei Jianhui Dong Xuyong Sun Xuyong Sun Xuyong Sun |
| author_facet | Ning Wen Ning Wen Ning Wen Jihua Wu Jihua Wu Jihua Wu Haibin Li Haibin Li Haibin Li Jixiang Liao Liugen Lan Xiawei Yang Guangyi Zhu Zhiying Lei Jianhui Dong Xuyong Sun Xuyong Sun Xuyong Sun |
| author_sort | Ning Wen |
| collection | DOAJ |
| description | Background: The role of the cellular level in kidney transplant rejection is unclear, and single-cell RNA sequencing (scRNA-seq) can reveal the single-cell landscape behind rejection of human kidney allografts at the single-cell level.Methods: High-quality transcriptomes were generated from scRNA-seq data from five human kidney transplantation biopsy cores. Cluster analysis was performed on the scRNA-seq data by known cell marker genes in order to identify different cell types. In addition, pathways, pseudotime developmental trajectories and transcriptional regulatory networks involved in different cell subpopulations were explored. Next, we systematically analyzed the scoring of gene sets regarding single-cell expression profiles based on biological processes associated with oxidative stress.Results: We obtained 81,139 single cells by scRNA-seq from kidney transplant tissue biopsies of three antibody-mediated rejection (ABMR) patients and two acute kidney injury (AKI) patients with non-rejection causes and identified 11 cell types, including immune cells, renal cells and several stromal cells. Immune cells such as macrophages showed inflammatory activation and antigen presentation and complement signaling, especially in rejection where some subpopulations of cells specifically expressed in rejection showed specific pro-inflammatory responses. In addition, patients with rejection are characterized by an increased number of fibroblasts, and further analysis of subpopulations of fibroblasts revealed their involvement in inflammatory and fibrosis-related pathways leading to increased renal rejection and fibrosis. Notably, the gene set score for response to oxidative stress was higher in patients with rejection.Conclusion: Insight into histological differences in kidney transplant patients with or without rejection was gained by assessing differences in cellular levels at single-cell resolution. In conclusion, we applied scRNA-seq to rejection after renal transplantation to deconstruct its heterogeneity and identify new targets for personalized therapeutic approaches. |
| first_indexed | 2024-03-12T22:51:17Z |
| format | Article |
| id | doaj.art-a84b52ba70ca42b89952700ce73b43b9 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-03-12T22:51:17Z |
| publishDate | 2023-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-a84b52ba70ca42b89952700ce73b43b92023-07-20T11:35:32ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2023-07-011110.3389/fcell.2023.12085661208566Immune landscape in rejection of renal transplantation revealed by high-throughput single-cell RNA sequencingNing Wen0Ning Wen1Ning Wen2Jihua Wu3Jihua Wu4Jihua Wu5Haibin Li6Haibin Li7Haibin Li8Jixiang Liao9Liugen Lan10Xiawei Yang11Guangyi Zhu12Zhiying Lei13Jianhui Dong14Xuyong Sun15Xuyong Sun16Xuyong Sun17Transplant Medical Center, The Second Affiliated Hospital of Guangxi Medical University, Nanning, ChinaGuangxi Key Laboratory of Organ Donation and Transplantation, Nanning, ChinaGuangxi Clinical Research Center for Organ Transplantation, Nanning, ChinaTransplant Medical Center, The Second Affiliated Hospital of Guangxi Medical University, Nanning, ChinaGuangxi Key Laboratory of Organ Donation and Transplantation, Nanning, ChinaGuangxi Clinical Research Center for Organ Transplantation, Nanning, ChinaTransplant Medical Center, The Second Affiliated Hospital of Guangxi Medical University, Nanning, ChinaGuangxi Key Laboratory of Organ Donation and Transplantation, Nanning, ChinaGuangxi Clinical Research Center for Organ Transplantation, Nanning, ChinaTransplant Medical Center, The Second Affiliated Hospital of Guangxi Medical University, Nanning, ChinaTransplant Medical Center, The Second Affiliated Hospital of Guangxi Medical University, Nanning, ChinaTransplant Medical Center, The Second Affiliated Hospital of Guangxi Medical University, Nanning, ChinaTransplant Medical Center, The Second Affiliated Hospital of Guangxi Medical University, Nanning, ChinaTransplant Medical Center, The Second Affiliated Hospital of Guangxi Medical University, Nanning, ChinaTransplant Medical Center, The Second Affiliated Hospital of Guangxi Medical University, Nanning, ChinaTransplant Medical Center, The Second Affiliated Hospital of Guangxi Medical University, Nanning, ChinaGuangxi Key Laboratory of Organ Donation and Transplantation, Nanning, ChinaGuangxi Clinical Research Center for Organ Transplantation, Nanning, ChinaBackground: The role of the cellular level in kidney transplant rejection is unclear, and single-cell RNA sequencing (scRNA-seq) can reveal the single-cell landscape behind rejection of human kidney allografts at the single-cell level.Methods: High-quality transcriptomes were generated from scRNA-seq data from five human kidney transplantation biopsy cores. Cluster analysis was performed on the scRNA-seq data by known cell marker genes in order to identify different cell types. In addition, pathways, pseudotime developmental trajectories and transcriptional regulatory networks involved in different cell subpopulations were explored. Next, we systematically analyzed the scoring of gene sets regarding single-cell expression profiles based on biological processes associated with oxidative stress.Results: We obtained 81,139 single cells by scRNA-seq from kidney transplant tissue biopsies of three antibody-mediated rejection (ABMR) patients and two acute kidney injury (AKI) patients with non-rejection causes and identified 11 cell types, including immune cells, renal cells and several stromal cells. Immune cells such as macrophages showed inflammatory activation and antigen presentation and complement signaling, especially in rejection where some subpopulations of cells specifically expressed in rejection showed specific pro-inflammatory responses. In addition, patients with rejection are characterized by an increased number of fibroblasts, and further analysis of subpopulations of fibroblasts revealed their involvement in inflammatory and fibrosis-related pathways leading to increased renal rejection and fibrosis. Notably, the gene set score for response to oxidative stress was higher in patients with rejection.Conclusion: Insight into histological differences in kidney transplant patients with or without rejection was gained by assessing differences in cellular levels at single-cell resolution. In conclusion, we applied scRNA-seq to rejection after renal transplantation to deconstruct its heterogeneity and identify new targets for personalized therapeutic approaches.https://www.frontiersin.org/articles/10.3389/fcell.2023.1208566/fullrenal transplantationrejectionsingle-cell RNA sequencingimmune landscapepro-inflammatory responseoxidative stress |
| spellingShingle | Ning Wen Ning Wen Ning Wen Jihua Wu Jihua Wu Jihua Wu Haibin Li Haibin Li Haibin Li Jixiang Liao Liugen Lan Xiawei Yang Guangyi Zhu Zhiying Lei Jianhui Dong Xuyong Sun Xuyong Sun Xuyong Sun Immune landscape in rejection of renal transplantation revealed by high-throughput single-cell RNA sequencing Frontiers in Cell and Developmental Biology renal transplantation rejection single-cell RNA sequencing immune landscape pro-inflammatory response oxidative stress |
| title | Immune landscape in rejection of renal transplantation revealed by high-throughput single-cell RNA sequencing |
| title_full | Immune landscape in rejection of renal transplantation revealed by high-throughput single-cell RNA sequencing |
| title_fullStr | Immune landscape in rejection of renal transplantation revealed by high-throughput single-cell RNA sequencing |
| title_full_unstemmed | Immune landscape in rejection of renal transplantation revealed by high-throughput single-cell RNA sequencing |
| title_short | Immune landscape in rejection of renal transplantation revealed by high-throughput single-cell RNA sequencing |
| title_sort | immune landscape in rejection of renal transplantation revealed by high throughput single cell rna sequencing |
| topic | renal transplantation rejection single-cell RNA sequencing immune landscape pro-inflammatory response oxidative stress |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2023.1208566/full |
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