Immune landscape in rejection of renal transplantation revealed by high-throughput single-cell RNA sequencing

Ning Wen; Jihua Wu; Haibin Li; Jixiang Liao; Liugen Lan; Xiawei Yang; Guangyi Zhu; Zhiying Lei; Jianhui Dong; Xuyong Sun

doi:10.3389/fcell.2023.1208566

Immune landscape in rejection of renal transplantation revealed by high-throughput single-cell RNA sequencing

Front Cell Dev Biol. 2023 Jul 20:11:1208566. doi: 10.3389/fcell.2023.1208566. eCollection 2023.

Authors

Ning Wen^{1

2

3}, Jihua Wu^{1

2

3}, Haibin Li^{1

2

3}, Jixiang Liao¹, Liugen Lan¹, Xiawei Yang¹, Guangyi Zhu¹, Zhiying Lei¹, Jianhui Dong¹, Xuyong Sun^{1

2

3}

Affiliations

¹ Transplant Medical Center, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China.
² Guangxi Key Laboratory of Organ Donation and Transplantation, Nanning, China.
³ Guangxi Clinical Research Center for Organ Transplantation, Nanning, China.

Abstract

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.

Keywords: immune landscape; oxidative stress; pro-inflammatory response; rejection; renal transplantation; single-cell RNA sequencing.

Grants and funding

This study was supported by the High-Level Medical Expert Training Program of Guangxi “139” Plan Funding (G202002016), Guangxi University Young and Middle-aged Teachers’ Scientific Research Basic Ability Improvement Project (2022ky0077).