Single-cell RNA sequencing reveals the transcriptomic landscape of kidneys in patients with ischemic acute kidney injury.
10.1097/CM9.0000000000002679
- Author:
Rong TANG
1
;
Peng JIN
2
;
Chanjuan SHEN
3
;
Wei LIN
4
;
Leilin YU
1
;
Xueling HU
1
;
Ting MENG
1
;
Linlin ZHANG
1
;
Ling PENG
1
;
Xiangcheng XIAO
1
;
Peter EGGENHUIZEN
5
;
Joshua D OOI
1
;
Xueqin WU
6
;
Xiang DING
2
;
Yong ZHONG
1
Author Information
1. Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
2. Department of Organ Transplantation, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
3. Department of Hematology, The Affiliated Zhuzhou Hospital Xiangya Medical College, Central South University, Zhuzhou, Hunan 412007, China.
4. Key Laboratory of Biological Nanotechnology of National Health Commission, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
5. Department of Medicine, Centre for Inflammatory Diseases, Monash Medical Centre, Monash University, Clayton, VIC 3168, Australia.
6. Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China.
- Publication Type:Journal Article
- MeSH:
Humans;
Mice;
Animals;
Transcriptome/genetics*;
Ligands;
Kidney/metabolism*;
Acute Kidney Injury/metabolism*;
Ischemia/metabolism*;
Reperfusion Injury/metabolism*;
Sequence Analysis, RNA;
Adaptor Proteins, Signal Transducing/metabolism*;
Tumor Suppressor Proteins/metabolism*
- From:
Chinese Medical Journal
2023;136(10):1177-1187
- CountryChina
- Language:English
-
Abstract:
BACKGROUND:Ischemic acute kidney injury (AKI) is a common syndrome associated with considerable mortality and healthcare costs. Up to now, the underlying pathogenesis of ischemic AKI remains incompletely understood, and specific strategies for early diagnosis and treatment of ischemic AKI are still lacking. Here, this study aimed to define the transcriptomic landscape of AKI patients through single-cell RNA sequencing (scRNA-seq) analysis in kidneys.
METHODS:In this study, scRNA-seq technology was applied to kidneys from two ischemic AKI patients, and three human public scRNA-seq datasets were collected as controls. Differentially expressed genes (DEGs) and cell clusters of kidneys were determined. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, as well as the ligand-receptor interaction between cells, were performed. We also validated several DEGs expression in kidneys from human ischemic AKI and ischemia/reperfusion (I/R) injury induced AKI mice through immunohistochemistry staining.
RESULTS:15 distinct cell clusters were determined in kidney from subjects of ischemic AKI and control. The injured proximal tubules (PT) displayed a proapoptotic and proinflammatory phenotype. PT cells of ischemic AKI had up-regulation of novel pro-apoptotic genes including USP47 , RASSF4 , EBAG9 , IER3 , SASH1 , SEPTIN7 , and NUB1 , which have not been reported in ischemic AKI previously. Several hub genes were validated in kidneys from human AKI and renal I/R injury mice, respectively. Furthermore, PT highly expressed DEGs enriched in endoplasmic reticulum stress, autophagy, and retinoic acid-inducible gene I (RIG-I) signaling. DEGs overexpressed in other tubular cells were primarily enriched in nucleotide-binding and oligomerization domain (NOD)-like receptor signaling, estrogen signaling, interleukin (IL)-12 signaling, and IL-17 signaling. Overexpressed genes in kidney-resident immune cells including macrophages, natural killer T (NKT) cells, monocytes, and dendritic cells were associated with leukocyte activation, chemotaxis, cell adhesion, and complement activation. In addition, the ligand-receptor interactions analysis revealed prominent communications between macrophages and monocytes with other cells in the process of ischemic AKI.
CONCLUSION:Together, this study reveals distinct cell-specific transcriptomic atlas of kidney in ischemic AKI patients, altered signaling pathways, and potential cell-cell crosstalk in the development of AKI. These data reveal new insights into the pathogenesis and potential therapeutic strategies in ischemic AKI.
