Single-cell RNA-seq with spatial transcriptomics to create an atlas of human diabetic kidney disease

被引:24
作者
Chen, Duo [1 ]
Shao, Mingwei [2 ]
Song, Yi [1 ]
Ren, Gaofei [2 ]
Guo, Feng [2 ]
Fan, Xunjie [1 ]
Wang, Yanyan [1 ]
Zhang, Wei [1 ]
Qin, Guijun [2 ,3 ]
机构
[1] Zhengzhou Univ, Inst Clin Med, Affiliated Hosp 1, Zhengzhou, Peoples R China
[2] Zhengzhou Univ, Dept Internal Med, Div Endocrinol, Affiliated Hosp 1, Zhengzhou, Peoples R China
[3] Zhengzhou Univ, Affiliated Hosp 1, Dept Internal Med, Div Endocrinol, 1 East Jianshe Rd, Zhengzhou 450052, Henan, Peoples R China
基金
中国国家自然科学基金;
关键词
diabetes mellitus; diabetic kidney disease; kidney; single-cell RNA sequence; spatial transcriptomics; GENE-EXPRESSION; MECHANISMS; COMPLICATIONS; NEPHROPATHY; DIAGNOSIS; RECEPTOR; THERAPY; GLUCOSE;
D O I
10.1096/fj.202202013RR
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Diabetic kidney disease (DKD) develops in similar to 40% of patients with diabetes and is the leading cause of chronic kidney disease worldwide. We used single--cell RNA-sequencing and spatial transcriptomic analyses of kidney specimens from patients with DKD. Unsupervised clustering revealed distinct cell clusters, including epithelial cells and fibroblasts. We also identified differentially expressed genes (DEGs) and assessed enrichment, and cell-cell interactions. Specific enrichment of DKD was evident in venous endothelial cells (VECs) and fibroblasts with elevated CCL19 expression. The DEGs in most kidney parenchymal cells in DKD were primarily enriched in inflammatory signaling pathways. Intercellular crosstalk revealed that most cell interactions in DKD are associated with chemokines. Spatial transcriptomics revealed that VECs co-localized with fibroblasts, with most immune cells being enriched in areas of renal fibrosis. These results provided insight into the cell populations, intercellular interactions, and signaling pathways underlying the pathogenesis and potential targets for treating DKD.
引用
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页数:13
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