Single-cell analysis reveals immune landscape in kidneys of patients with chronic transplant rejection
| Autor: | Ming Li, Ding Liu, Liuyang Li, Anqi Lin, Li-pei Fan, Zefeng Guo, Yuzhu Li, Shichao Li, Jianmin Hu, Yong-guang Liu, Ming Zhao, Siqiang Yang, Ying Guo, Song Zhou, Guorong Liao, Hua Chen, Jun Liao |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Graft Rejection Male Cell type Stromal cell CD14 030232 urology & nephrology Chronic kidney transplant rejection Medicine (miscellaneous) Biology Kidney Single-cell RNA sequencing Graft 03 medical and health sciences 0302 clinical medicine Immune system Single-cell analysis medicine Cytotoxic T cell Cluster Analysis Humans Gene Regulatory Networks Renal Insufficiency Chronic Pharmacology Toxicology and Pharmaceutics (miscellaneous) B-Lymphocytes Sequence Analysis RNA Gene Expression Profiling Immune landscape medicine.disease Kidney Transplantation Transplant rejection Killer Cells Natural 030104 developmental biology Case-Control Studies Cancer research Female Single-Cell Analysis CD8 Research Paper |
| Zdroj: | Theranostics |
| ISSN: | 1838-7640 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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