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Multimodal single cell sequencing implicates chromatin accessibility and genetic background in diabetic kidney disease progression

ABSTRACT: Multimodal single cell sequencing implicates chromatin accessibility and genetic background in diabetic kidney disease progression

PROVIDER: PRJNA800746 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17764600_1.fastq.gz	Fastqsanger.gz
	SRR17764600_2.fastq.gz	Fastqsanger.gz
	SRR17764601_1.fastq.gz	Fastqsanger.gz
	SRR17764601_2.fastq.gz	Fastqsanger.gz
	SRR17764602_1.fastq.gz	Fastqsanger.gz

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Multimodal single cell sequencing implicates chromatin accessibility and genetic background in diabetic kidney disease progression

Project description:Purpose: Single cell sequencing has advanced our understanding of kidney biology. The goals of this study are to compare single nucleus RNA (snRNA-seq) and single nucleus assay for transposase accessible chromatin sequencing (snATAC-seq) from healthy control donors and donors with type 2 diabetic kidney disease to identify altered signaling pathways and chromatin accessibility patterns observed in diabetic kidney disease. Methods: Nuclear dissociation of human kidney cortex samples was performed on samples obtained from patients undergoing tumor nephrectromy or deceased organ donors. snRNA-seq and snATAC-seq libraries were prepared using 10X Genomics kits according to manufacturers instructions. For this study, two healthy control libraries from one donor were prepared with the following chemistries (1 - single cell 3-prime v3, 1 - single cell ATAC v1) and nine DKD libraries from seven donors were prepared with the following chemistries (2 - single cell 5-prime v2 paired-end, 7 - single cell ATAC v1). Raw data for three healthy control and three DKD snRNA-seq libraries sequenced with single nucleus 5-prime R2 only can be found in GSE13188213. Raw data for two healthy control snRNA-seq sequenced with single nucleus 5-prime paired-end and five snATAC-seq single nucleus ATAC v1 libraries can be found in GSE151302. snRNA-seq and snATAC-seq libraries from these earlier studies were recounted with cellranger (v4.0) or cellranger-atac (v2.0) to provide consistency across processed data files.

2022-07-28 | GSE195460 | GEO

Multimodal single cell sequencing of human diabetic kidney disease implicates chromatin accessibility and genetic background in disease progression [cut-and-run and bulk ATAC-seq to support single cell data]

Project description:Multimodal single cell sequencing of human diabetic kidney disease implicates chromatin accessibility and genetic background in disease progression [cut-and-run and bulk ATAC-seq to support single cell data]

| PRJNA800684 | ENA

Multimodal single cell sequencing implicates chromatin accessibility and genetic background in diabetic kidney disease progression.

Project description:The proximal tubule is a key regulator of kidney function and glucose metabolism. Diabetic kidney disease leads to proximal tubule injury and changes in chromatin accessibility that modify the activity of transcription factors involved in glucose metabolism and inflammation. Here we use single nucleus RNA and ATAC sequencing to show that diabetic kidney disease leads to reduced accessibility of glucocorticoid receptor binding sites and an injury-associated expression signature in the proximal tubule. We hypothesize that chromatin accessibility is regulated by genetic background and closely-intertwined with metabolic memory, which pre-programs the proximal tubule to respond differently to external stimuli. Glucocorticoid excess has long been known to increase risk for type 2 diabetes, which raises the possibility that glucocorticoid receptor inhibition may mitigate the adverse metabolic effects of diabetic kidney disease.

| S-EPMC9448792 | biostudies-literature

Project description:Purpose: Identification of glucocorticoid recepor binding sites on human kidney proximal tubular cells to better understand epigenetic alterations in diabetic kidney diseases Methods: CUT&RUN assay libraries for cultured cells or human kidneys were generated with the CUTANA kit (EpiCypher, 14-1048). 500,000 cells were mixed and incubated with Concanavalin A (ConA) conjugated paramagnetic beads. Antibodies to the glucocorticoid receptor were added to target samples and IgG was added to negative controls. The remaining steps were performed according to manufacturer’s instructions. Library preparation was performed using the NEBNext Ultra II DNA Library Prep Kit for Illumina (New England BioLabs, E7645S) with manufacturer’s instructions, including minor modifications indicated by CUTANA described above. CUT&RUN libraries were sequenced on a NovaSeq instrument (Illumina, 150 bp paired-end reads). For bulk ATAC-seq, 50,000 nuclei were transposed in 25 μL of ATAC-seq transposition mix [12.5 μL 2× Illumina Tagment DNA (TD) buffer; 10.5 μL nuclease-free water; 2.0 μL Tn5 transposase (Illumina/Nextera, FC-121-1030)] and incubated at 37°C for 1 h on a thermomixer. The transposed DNA was purified with QIAGEN MinElute kit (28004) and amplified with dual indexes.

2022-07-28 | GSE195443 | GEO

Diabetic vs. Menopausal/diabetic kidney cortex

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

Diabetic vs. Menopausal/diabetic kidney cortex

2010-09-14 | GSE20702 | GEO

Comparative RNA-Seq transcriptome analyses of diabetic nerve and kidney disease II

Project description:Diabetic kidney disease (DKD) and diabetic peripheral neuropathy (DPN) are common complications of type 1 (T1D) and type 2 (T2D) diabetes. However, the mechanisms underlying the development and progression of these complications are unclear. Thus, the goal of the current study was to use system biology approaches to examine DKD and DPN pathogenesis in T1D and T2D mouse models on the same genetic background. We optimized a streptozotocin-induced db/+ murine model of T1D and compared it to our established db/db T2D mouse model of the same C57BLKS/J background and confirmed both develop DKD and DPN. Transcriptomic data from glomeruli and sciatic nerve tissue from T1D and T2D mice were analyzed by self-organizing map and differential gene expression analysis followed by functional enrichment. Consistent with prior literature, pathways related to immune function and inflammation were dysregulated in both DKD and DPN in T1D and T2D mice. The gene-level analysis identified a high degree of concordance in DEGs in both DKD and DPN and across diabetes type, suggesting genetic background influences diabetic complications. These findings offer new insight as the influence of genetic background on DPN in mouse models has not been well defined. Collectively, these findings support the role of inflammation and genetic background in complications of both T1D and T2D.

2023-09-08 | GSE222776 | GEO

Transcriptome Analysis of Human Diabetic Kidney Disease

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

Expression data from OVE26 diabetic mouse kidney

Project description:OVE26 mouse was chosen to study the progressive changes in renal gene expression because it displays the most advanced albuminuria mouse models that assembles advanced human diabetic nephropathy. OVE26 mice induce inflammatory gene expression changes consistent with advanced renal disease, associated with severe albuminuria and not reported in any other diabetic models. They provide the first opportunity in a model of diabetic nephropathy to assess the effect of induction of inflammatory proteins that have been implicated in renal injury. Microarray expression was performed on whole kidney from control and diabetic mice at 2, 4 and 8 months of age and validated by rtPCR, in situ hybridization or immunohistochemistry.

2010-04-06 | E-GEOD-20636 | biostudies-arrayexpress

RNA-Seq of Kidney Glomeruli from Type 2 diabetic (db/db) and non-diabetic mice

Project description:We investigated the gene expression profiles of RNA isolated from kidney glomeruli from aged, 25 week old type-2 diabetic (db/db) and non-diabetic mice. In order to investigate the consequences of hyperglycemia on the pathogenesis and progression of diabetic nephropathy Kidney glomeruli from 3 diabetic and 3 non-diabetic, control mice were isolated and RNA purified for RNA-Seq analysis on the Illumina HiSeq 2000. The goal of the project was to generate comprehensive list of noncoding RNA genes differentially regulated between the two conditions in order to identify novel targets for further study.

2016-10-24 | E-GEOD-77717 | biostudies-arrayexpress

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