Theranostics 2020; 10(19):8851-8862. doi:10.7150/thno.48201 This issue Cite

Research Paper

Single-cell analysis reveals immune landscape in kidneys of patients with chronic transplant rejection

Yongguang Liu*, Jianmin Hu*, Ding Liu, Song Zhou, Jun Liao, Guorong Liao, Siqiang Yang, Zefeng Guo, Yuzhu Li, Shichao Li, Hua Chen, Ying Guo, Ming Li, Lipei Fan, Liuyang Li, Anqi Lin, Ming Zhao

Department of Organ Transplantation, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
*These authors contributed equally to this work.

Citation:
Liu Y, Hu J, Liu D, Zhou S, Liao J, Liao G, Yang S, Guo Z, Li Y, Li S, Chen H, Guo Y, Li M, Fan L, Li L, Lin A, Zhao M. Single-cell analysis reveals immune landscape in kidneys of patients with chronic transplant rejection. Theranostics 2020; 10(19):8851-8862. doi:10.7150/thno.48201. https://www.thno.org/v10p8851.htm
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Abstract

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Rationale: Single-cell RNA sequencing (scRNA-seq) has provided an unbiased assessment of specific profiling of cell populations at the single-cell level. Conventional renal biopsy and bulk RNA-seq only average out the underlying differences, while the extent of chronic kidney transplant rejection (CKTR) and how it is shaped by cells and states in the kidney remain poorly characterized. Here, we analyzed cells from CKTR and matched healthy adult kidneys at single-cell resolution.

Methods: High-quality transcriptomes were generated from three healthy human kidneys and two CKTR biopsies. Unsupervised clustering analysis of biopsy specimens was performed to identify fifteen distinct cell types, including major immune cells, renal cells and a few types of stromal cells. Single-sample gene set enrichment (ssGSEA) algorithm was utilized to explore functional differences between cell subpopulations and between CKTR and normal cells.

Results: Natural killer T (NKT) cells formed five subclasses, representing CD4+ T cells, CD8+ T cells, cytotoxic T lymphocytes (CTLs), regulatory T cells (Tregs) and natural killer cells (NKs). Memory B cells were classified into two subtypes, representing reverse immune activation. Monocytes formed a classic CD14+ group and a nonclassical CD16+ group. We identified a novel subpopulation [myofibroblasts (MyoF)] in fibroblasts, which express collagen and extracellular matrix components. The CKTR group was characterized by increased numbers of immune cells and MyoF, leading to increased renal rejection and fibrosis.

Conclusions: By assessing functional differences of subtype at single-cell resolution, we discovered different subtypes that correlated with distinct functions in CKTR. This resource provides deeper insights into CKTR biology that will be helpful in the diagnosis and treatment of CKTR.

Keywords: Chronic kidney transplant rejection, Single-cell RNA sequencing, Immune landscape, Kidney, Graft


Citation styles

APA
Liu, Y., Hu, J., Liu, D., Zhou, S., Liao, J., Liao, G., Yang, S., Guo, Z., Li, Y., Li, S., Chen, H., Guo, Y., Li, M., Fan, L., Li, L., Lin, A., Zhao, M. (2020). Single-cell analysis reveals immune landscape in kidneys of patients with chronic transplant rejection. Theranostics, 10(19), 8851-8862. https://doi.org/10.7150/thno.48201.

ACS
Liu, Y.; Hu, J.; Liu, D.; Zhou, S.; Liao, J.; Liao, G.; Yang, S.; Guo, Z.; Li, Y.; Li, S.; Chen, H.; Guo, Y.; Li, M.; Fan, L.; Li, L.; Lin, A.; Zhao, M. Single-cell analysis reveals immune landscape in kidneys of patients with chronic transplant rejection. Theranostics 2020, 10 (19), 8851-8862. DOI: 10.7150/thno.48201.

NLM
Liu Y, Hu J, Liu D, Zhou S, Liao J, Liao G, Yang S, Guo Z, Li Y, Li S, Chen H, Guo Y, Li M, Fan L, Li L, Lin A, Zhao M. Single-cell analysis reveals immune landscape in kidneys of patients with chronic transplant rejection. Theranostics 2020; 10(19):8851-8862. doi:10.7150/thno.48201. https://www.thno.org/v10p8851.htm

CSE
Liu Y, Hu J, Liu D, Zhou S, Liao J, Liao G, Yang S, Guo Z, Li Y, Li S, Chen H, Guo Y, Li M, Fan L, Li L, Lin A, Zhao M. 2020. Single-cell analysis reveals immune landscape in kidneys of patients with chronic transplant rejection. Theranostics. 10(19):8851-8862.

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