A single-cell transcriptomic atlas characterizes the kidney in the diabetic kidney disease
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ABSTRACT:
PROVIDER: PRJNA862452 | ENA |
REPOSITORIES: ENA
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Project description:Diabetic kidney disease (DKD), a common and devastating microvascular complication of diabetes, is the leading cause of end-stage renal disease (ESRD). Since mechanisms of kidney injury in DKD were largely unknown, we performed single-cell RNA sequencing (scRNA-seq) on human kidneys collected from 3 DKD and 3 normal samples using 10×Genomics. In our study, a total of 51315 cells were enrolled for analyses and nine kidney cell types and seven immune cell types were identified. The cell-type-specific changes in gene expression and signaling pathways of podocyte, mesangial cells, endothelial cells, proximal tubule and macrophages indicate abnormal regulation associated with inflammation, apoptosis, oxidative stress, extracelluar matrix accumulation, and immune activation. In particular, we show that podocytes and renal tubular epithelial cells have a tremendous capacity to regenerate, which is involved in the repairment of injury. And extracellular vesicles, an important mediator of intercellular communication, might play a vital role for this progress. Besides, we identified new candidate transcription factors responsible for the progression of DKD. We also revealed a M1-M2 hybrid pattern, in which M1 and M2 are coupled activation in macrophages of DKD. Furthermore, we demonstrated a complex intercellular interaction between kidney cells and kidney cells or kidney cells and immune cells. Thus, our study will further the understanding of DKD pathogenesis and provide novel therapeutic targets for its treatment in the future.
2025-01-07 | GSE209781 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE30528: Transcriptome Analysis of Human Diabetic Kidney Disease (DKD Glomeruli vs. Control Glomeruli) GSE30529: Transcriptome Analysis of Human Diabetic Kidney Disease (DKD Tubuli vs. Control Tubuli) GSE30566: Transcriptome Analysis of Human Diabetic Kidney Disease (Control Glomeruli vs. Control Tubuli) Refer to individual Series
2011-08-02 | E-GEOD-30122 | biostudies-arrayexpress
Project description:Bypass and diabetic kidney disease
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Project description:Aim: To compare transcriptomic profiles of kidney cortex between healthy db/m mice, and mice with early stage diabetic kidney disease (uninephrectomized db/db injected with LacZAAV) and advanced stage diabetic kidney disease (uninephrectomized db/db mice injected with ReninAAV) Methods: Bulk RNA sequecing using the Illumina NextSeq 500 platform. Results: We identified 5,500 differentially expressed genes (DEGs) in db/db UNx LacZAVV mice compared to healthy controls, and 4,470 DEGs were identified in db/db UNx ReninAAV mice compared to healthy controls. Also, we showed in supplementery files that 3,039 DEGs were identified between db/db UNx LacZAAV mice and db/db UNx ReninAAV mice. Conclusion: We identified several gene expression changes in our two animal models of diabetic kidney disease.
2021-10-24 | GSE185616 | GEO
Project description:Mouse models have been widely used to understand kidney disease pathomechanisms and play an important role in drug discovery. However, these models have not been systematically analyzed and compared. We analyzed single-cell RNA sequencing data (36 samples) and bulk gene expression data (42 samples) from 18 commonly used mouse kidney disease models. We compared single-nucleus RNA sequencing data from a mouse diabetic kidney disease model with data from patients with diabetic kidney disease and healthy controls. We generated a uniformly processed mouse single-cell atlas containing information for nearly 300,000 cells, identifying all major kidney cell types and states. Our analysis revealed that changes in fractions of cell types are major drivers of differences in bulk gene expression. Although gene expression changes at the single-cell level were mostly model-specific, different disease models showed similar changes when compared at a pathway level. Tensor decomposition analysis highlighted the important changes in proximal tubule cells in disease states. Specifically, we identified important alterations in expression of metabolic and inflammation-associated pathways. The mouse diabetic kidney disease model and patients with diabetic kidney disease shared only a small number of conserved cell type-specific differentially expressed genes, but we observed pathway-level activation patterns conserved between mouse and human diabetic kidney disease samples. This study provides a comprehensive mouse kidney single-cell atlas and defines gene expression commonalities and differences in disease states in mice. The results highlight the key role of cell heterogeneity in driving changes in bulk gene expression and the limited overlap of single-cell gene expression changes between animal models and patients, but they also reveal consistent pathway-level changes.
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Project description:In this study, we utilized the db/db, uninephrectomy and renin-hypertension mouse model. We compared vehicle to ACE inhibitor, Rosiglitizone, SGLT2 inhibitor, ACEi + Rosiglitizone and ACEi + SGLT2i at two time points (2 days and 2 weeks). We generated snRNA-seq datasets from all groups comprising nearly 1 million cells. Analysis of the resulting atlas revealed that the different medications affected strikingly different cell types. Combination therapy had the largest effects, but these effects were also largely non-overlapping. This study highlights the cellular complexity of diabetic nephropathy and the effects of different classes of therapy. The results support the development of combination therapies since different drug classes target different cell types in kidney.
2022-06-14 | GSE184652 | GEO
Project description:Gene expression in kidney cortex of diabetic mice and menopausal diabetic mice following 6 weeks of diabetes. Diabetes was induced with low-dose streptozotocin injections and menopause was induced by injection of 4-vinylcyclohexene diepoxide. Samples = 12
2010-09-14 | E-GEOD-20702 | biostudies-arrayexpress
Project description:Analysis of gene expression changes in differentiated human podocytes treated with the serum from patients with (DKD+) or without (DKD-) diabetic kidney disease when compared to normal subjects (C). The hypothesis is that the three groups can be distinghed by their differential gene expression pattern. The results obtained revealed important information regarding differences in gene expression in human podocytes treated with the serum from patients with (DKD+) or without (DKD-) diabetic kidney disease when compared to normal subjects (C). Human podocytes were contacted with the serum from patients with diabetes and kidney disease (DKD+) or without kidney disease (DKD-) and compared to normal human podocytes contacted with serum from patients without diabetes (C).
2013-07-11 | E-GEOD-46897 | biostudies-arrayexpress
Project description:Analysis of gene expression changes in differentiated human podocytes treated with the serum from patients with (DKD+) or without (DKD-) diabetic kidney disease when compared to normal subjects (C). The hypothesis is that the three groups can be distinghed by their differential gene expression pattern. The results obtained revealed important information regarding differences in gene expression in human podocytes treated with the serum from patients with (DKD+) or without (DKD-) diabetic kidney disease when compared to normal subjects (C). Human podocytes were contacted with the serum from patients with diabetes and kidney disease (DKD+) or without kidney disease (DKD-) and compared to normal human podocytes contacted with serum from patients without diabetes (C).
2013-07-13 | E-GEOD-46899 | biostudies-arrayexpress
Project description:Since the etiology of diabetic chronic kidney disease (CKD) is multifactorial, studies on DNA methylation for kidney function deterioration have rarely been performed despite the need for an epigenetic approach. Therefore, this study aimed to identify epigenetic markers associated with CKD progression based on the decline in the estimated glomerular filtration rate in diabetic CKD in Korea.
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