GEO DataSets

(Submitter supplied) Pancreatic beta-cell dysfunction and eventual beta-cell loss are key steps in the course of type 2 diabetes (T2D). Endoplasmic reticulum (ER) stress, in particular the PERK-ATF4 pathway, has been implicated in promoting these beta-cell pathologies. However, the exact molecular events surrounding the PERK-ATF4 pathway in beta-cell dysfunction remain unknown. Here, we discovered that ATF4 transcriptionally promotes expression of PDE4D, which results in beta-cell dysfunction via downregulation of cAMP signaling. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24247

8 Samples

Download data: TXT

(Submitter supplied) RNA sequencing on LNCaP cells was carried out to study how tunicamycin-induced gene expression is affected by knockdown of EIF2AK3 and ATF4.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

28 Samples

Download data: TXT

(Submitter supplied) We report the physiological role of ATF4 within mouse liver, under basal and ER stress conditions. With three mice per group, and approximately 30 million reads per sample, we obtained genome-wide role of ATF4 within the liver. We find ATF4 is responsible for a small subset of ER stress genes, and larger than previously thought basal subset.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL13112

12 Samples

Download data: TXT

(Submitter supplied) We applied GSIS, immunofluorescence staining, WB, and flow cytometry to observe the protective effects of C3G on palmitate-induced beta cell apoptosis and insulin deficiency, after which we explored the mechanism using RNA sequencing (RNA-seq) and quantitative real-time PCR (qPCR), and finally validated the mechanism using Western Blot (WB) and small interfering RNA (siRNA).The results of GSIS on both INS-1E cells and mouse primary islets plus a series of experiments related to cell apoptosis showed that C3G could restore the damage caused by lipotoxicity through promoting insulin secretion and alleviating cell apoptosis. more...

Organism:

Rattus norvegicus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL25947

9 Samples

Download data: TXT

(Submitter supplied) Chronic exposure to epinephrine enhances the compensatory insulin secretion in MIN6 cells while persistently inhibiting cell proliferation. The molecular mechanisms underlying these phenomena were investigated through transcriptome sequencing, which identified differential mRNA transcriptional expression. This analysis has uncovered the pivotal signaling pathways that govern cellular function and destiny.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24247

6 Samples

Download data: XLS, XLSX

(Submitter supplied) Objective Notch signaling is re-activated in β cells from obese mice, and is causal to β cell dysfunction. Notch activity is determined in part by expression of transmembrane ligand availability in a neighboring cell. We hypothesized that β cell expression of Jagged1 determines the maladaptive Notch response and resultant β cell dysfunction in obese mice. Methods We assessed expression of Notch pathway components in diet-induced obese (DIO) or leptin receptor-deficient (db/db) mice, and performed single cell RNA sequencing (scRNAseq) in islets from patients with and without type 2 diabetes (T2D). more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24247

6 Samples

Download data: TXT

(Submitter supplied) We tested >13,000 sequences containing each allele of 6,628 SNPs associated with altered in vivo chromatin accessibility in human islets and/or type 2 diabetes risk (T2D GWAS SNPs) for transcriptional activity in ß cell under steady state and endoplasmic reticulum (ER) stress conditions using the massively parallel reporter assay (MPRA).

Organism:

synthetic construct; Mus musculus

Type:

Other

Platforms:

GPL19057 GPL19424

9 Samples

Download data: FA, TXT

(Submitter supplied) The next-generation-sequencing (NGS) of ribosome footprintings and poly(A) enriched RNA-seq have been proformed to examine transcriptional and translational changes in an mouse insulinoma cell MIN6 under acute and chronic endoplasmic reticular stresses.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing; Other

Platform:

GPL13112

18 Samples

Download data: TXT

(Submitter supplied) Activating Transcription Factor 4 (ATF4) is a transcription factor that regulates cellular responses to nutrient deficiency, endoplasmic reticulum stress and oxidative stress. At the organism level, it is implicated in processes such as hematopoiesis, skeletogenesis, eye development, memory, muscle atrophy, and carbohydrate and lipid metabolism. Here, we carried out a massively parallel reporter assay (MPRA) to identify allelic regulatory effects of human genetic variants that reside in ATF4 binding sites identified in ChIP-Seq experiments.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

14 Samples

Download data: TSV

(Submitter supplied) Diabetes mellitus (DM) is a chronic disease associated with elevated blood glucose level and resulting from a loss of functional beta-cell mass. The goal of this study is to investigate the response of human pancreatic cells to pathophysiological conditions associated with beta-cell dysfunction, ultimately to identify molecular mechanisms contributing to the development of diabetes. Isolated primary human islets from three non-diabetic donors were exposed in vitro to pro-inflammatory, oxidative, metabolic and endoplasmic reticulum stress for up to 3 days. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

5 Samples

Download data: CSV, MTX, TSV, XLSX

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL19057 GPL17021

6 Samples

Download data: MTX, TSV

(Submitter supplied) To investigate the function of Opa1 in the regulation of adult neurogenesis, we created a conditional Opa1-knockout mouse line by cross-breeding Nestin-CreERT2;ROSA26YFP mice with Opa1-Flox mice. Using Tamoxifen, we induced Opa1 knockout on 8-weeks-old Nestin-CreERT2;ROSA26YFP;Opa1-Flox mice. We then sorted YFP-positive cells from the hippocampus using flow cytometry at 10 weeks. RNA was extracted from sorted cells and subjected to next generation sequencing.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

4 Samples

Download data: XLSX

(Submitter supplied) To investigate the function of Opa1 in the regulation of adult neurogenesis, we created a conditional Opa1-knockout mouse line by cross-breeding Nestin-CreERT2;ROSA26YFP mice with Opa1-Flox mice.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL19057

2 Samples

Download data: MTX, TSV

(Submitter supplied) To understand the contributions of the Integrated Stress Response (ISR) to the axon regenerative and neurodegenerative transcriptional programs activated by axon injury in the CNS, we evaluated by RNA-seq the retinal transcriptomes of conditional knockout mouse lines for components of the ISR three days after optic nerve crush injury. Prior to injury, intravitreal injection of AAV2-mTagBFP2-ires-Cre under the control of the human synapsin-1 promoter facilitated neuron-specific knockout of Eif2ak3, the gene that encodes the ER stress-responsive kinase Perk; Atf4, the gene that encodes the ISR mediator Activating transcription factor-4; or Ddit3, the gene that encodes another transcription factor that can mediate the ISR, C/ebp homologous protein, or CHOP. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24247

23 Samples

Download data: TXT

(Submitter supplied) To investigate a role of UCP2 in pancreatic β-cells, we performed whole genome microarray in islets from βUCP2Tg mice, which overexpressed UCP2 in specifically β-cells.

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL21163

8 Samples

Download data: TXT

(Submitter supplied) Type 2 diabetes (T2D) is associated with defective insulin secretion, reduced β-cell mass, and β-cell dedifferentiation. Aldehyde dehydrogenase 1 isoform A3 (ALHD1A3) serves as a marker of β-cell dedifferentiation and correlates with T2D progression. ALDH1A3-positive β-cells (A+) demonstrate impaired insulin secretion, and their numbers decrease when diabetic mice are rendered euglycemic by pair-feeding. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24247

7 Samples

Download data: TXT

(Submitter supplied) We used single cell multiome (ATAC and RNA) sequencing to profile 85266 islet cells from 20 individuals, including islets from non-diabetic, pre-diabetic and type 2 diabetic (T2D) donors. We characterize changes in regulatory programs of islet cell types and subtypes in T2D progression, describe the relationship of these programs to genetic risk for T2D, and use allelic imbalance mapping to define cell type-specific functions for candidate T2D causal variants.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL24676

40 Samples

Download data: CSV

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing; Genome variation profiling by genome tiling array; Expression profiling by high throughput sequencing

Platforms:

GPL16104 GPL24676

110 Samples

Download data: IDAT

(Submitter supplied) Genomic DNA was extracted from human islets using Dneasy Blood & Tissue Kit (QIAGEN) with RNase A treatment. 200-500ng DNA was genotyped using InfiniumOmni2-5-8v Genotyping BeadChips (Illumina).DNA was isolated from human islet cells from various donors. DNA was genotyped using Illumina Infinium whole-genome genotyping array. Genotypes were called with GenomeStudio (v.2.0.4) using default settings. Genotypes that passed quality filters (missing<0.05, minor allele frequency (MAF>0.01), non-ambiguous alleles defined by AT/GC variants with MAF>40%) were exported.

Organism:

Homo sapiens

Type:

Genome variation profiling by genome tiling array

Platform:

GPL16104

36 Samples

Download data: IDAT

(Submitter supplied) In this study, we used single cell nucleus ATAC-seq (snATAC-seq) to profile 218,973 islet cells from 34 individuals, including islets from non-diabetic, pre-diabetic and type 2 diectic (T2D) donors. We characterize changes in regulatory programs of islet cell types in T2D progression, describe the relationship of these programs to genetic risk for T2D, and use allelic imbalance mapping to define cell type-specific functions for candidate T2D causal variants.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL24676

34 Samples

Download data: CSV, RDATA