Mapping the daily rhythmic transcriptome in the diabetic retina
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA976271 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24739200_1.fastq.gz | Fastqsanger.gz | |||
| SRR24739200_2.fastq.gz | Fastqsanger.gz | |||
| SRR24739201_1.fastq.gz | Fastqsanger.gz | |||
| SRR24739201_2.fastq.gz | Fastqsanger.gz | |||
| SRR24739202_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 116 |
Similar Datasets
Project description:Retinal function changes dramatically from day to night. Yet, clinical diagnosis, treatments, and experimental sampling occur during the day, leaving a significant gap in our understanding of the pathobiology occurring at night. While there is evidence that diabetes disrupts the circadian system that optimizes our physiology to the environmental light/dark cycle, the impact of such disruption is not well understood. This study investigates whether diabetes affects the retina's daily rhythm of gene expression to understand the pathobiology of diabetic retinopathy, a common complication of diabetes. Control and hyperglycemic littermate mice (Ins2Akita/J) were kept under a standard 12h:12h light/dark cycle until four months of age. Bulk mRNA sequencing was conducted in retinas collected every 4 hours throughout the 24 hr light/dark cycle. Computational approaches were used to detect rhythmicity, predict acrophase, identify differential rhythmic patterns, analyze phase set enrichment, and predict upstream regulators. The retinal transcriptome exhibited a tightly regulated rhythmic expression with a clear 12-hr axis of transcriptional rush, peaking at midday and midnight. The functions of day-peaking genes were enriched for DNA repair, RNA splicing, and ribosomal protein synthesis, whereas night-peaking genes were enriched for metabolic processes and growth factor signaling. Although the 12-hr transcriptional axis is retained in the diabetic retina, it was phase advanced by approximately 1-3 hours with a wider distribution. Upstream regulator analysis for the genes that showed phase shifts identified oxygen sensing mechanisms and HIF1alpha as regulators, but not the circadian clock, which remained in phase to the light/dark cycle. We propose a model in which early in diabetes, the diabetic retina experiences a ‘jet lag’ caused by the entrained circadian clock and its output being in one phase and metabolic pathways related to neuronal dysfunction and hypoxia driving advancement of gene expression to a different phase. Further studies are now required to evaluate the chronic implications of such internal jet lag for development of diabetic retinopathy.
2023-05-31 | GSE233440 | GEO
Project description: Not available
| S-EPMC11330665 | biostudies-literature
Project description:The mammalian retina contains an endogenous circadian clock system, located in various cell types. This system enables timing of a broad range of essential retinal functions to anticipate daily changes in environmental lighting conditions. Furthermore, the circadian clocks appear to promote retinal health. A leading cause of blindness in developed countries is diabetic retinopathy. While it is clear that diabetes affects the master clock and its circadian output in the SCN, the effect of diabetic retinopathy on the retinal clock system is unknown. To investigate the influence of diabetic retinopathy on circadian regulation of the retina at a genome-wide level, microarray analysis was used to compare retinal transcriptomes between light- and dark-adapted non-diabetic and diabetic mice.
2021-09-05 | GSE151350 | GEO
Project description:Aging Reprograms the Rhythmic Transcriptome in the Retina
| PRJNA1281061 | ENA
Project description:Pericyte loss is an early and critical event in the pathogenesis of diabetic retinopathy (DR), yet the molecular mechanisms underlying pericyte dysfunction remain incompletely understood. Using single-cell RNA sequencing, we generated a retinal cellular overview comprising 37,982 cells from diabetic and non-diabetic mice. We identified a previously unrecognized pericyte subpopulation defined by high expression of pituitary tumor transforming gene 1 (PTTG1), which was enriched in diabetic retina. Functional studies demonstrated that CRISPR/Cas9- or siRNA-mediated silencing of PTTG1 restored pericyte stability and barrier-supporting function under high glucose stress. In vivo, PTTG1 silencing via viral or pericyte-specific AAV delivery improved retinal vascular integrity and reduced retinal vascular dysfunction in diabetic mice. Integrated transcriptomic and metabolomic profiling revealed that PTTG1 silencing reprogrammed metabolism, modulating glycolytic flux and attenuating oxidative stress.
2026-03-30 | MTBLS14184 | MetaboLights
Project description:<p> Pericyte loss is an early and critical event in the pathogenesis of diabetic retinopathy (DR), yet the molecular mechanisms underlying pericyte dysfunction remain incompletely understood. Using single-cell RNA sequencing, we generated a retinal cellular overview comprising 18,926 cells from diabetic and non-diabetic mice. We identified a previously unrecognized pericyte subpopulation defined by high expression of pituitary tumor transforming gene 1 (PTTG1), which was enriched in diabetic retina. Functional studies demonstrated that CRISPR/Cas9 or siRNA-mediated silencing of PTTG1 restored pericyte stability and barrier-supporting function under high-glucose stress. In vivo, knockdown of PTTG1 via lentiviral or pericyte-specific AAV delivery improved retinal vascular integrity and reduced retinal vascular function in diabetic mice. Integrated transcriptomic and metabolomic profiling revealed PTTG1 knockdown reprogrammed metabolism by modulating glycolytic flux and attenuating oxidative stress. Furthermore, a therapeutic strategy employing spherical nucleic acid-based siPTTG1 nanocarriers (sTDN-siPTTG1) significantly ameliorated retinal vascular dysfunction in DR model. These findings suggest that PTTG1 is a critical regulator of pericyte metabolic homeostasis and microvascular function in DR, highlighting its translational potential as a therapeutic target for diabetic microvascular complications. </p>
2026-03-27 | MTBLS13544 | MetaboLights
Project description:We employed LncRNA/mRNA expression profiling as a discovery platform identify aberrantly expressed LncRNAs that fail to reverse back after hyperglycemia is terminated. Using rat model of diabetic retinopathy- metabolic memory, LncRNA array was performed in the retina of rats diabetic for eight months, or in poor glycemic control for four months followed by good glycemic control for four additional months. Expression of selected LncRNAs and their associated genes from these profiles were confirmed by quantitative real-time PCR.
2024-11-27 | GSE251731 | GEO
Project description:Diabetic retinopathy (DR) is one of the main causes of blindness in working age populations in industrialized countries. It is estimated that close to 100 million individuals worldwide suffer from DR. Regrettably, relatively little is known of the cellular processes at play during late stages of the disease, especially concerning diabetic macular edema (DME). Streptozotocin-induced diabetic retinopathy (STZ) allows to reproduce experimentally in the mouse retina the retina vascular leakage and neuroegeneration features observed in human pathological retina with non-proliferative DR. Using agnostic and orthogonal approaches, in our work we demonstrate that in contrast to healthy retina, the STZ diabetic retina engages pathways of cell cycle arrest, resulting in cellular senescence. These findings combined with further pharmacological approaches provide mechanistic evidence supporting that targeting selectively senescent vessels in DR represents a potential treatment for high vascular permeability in DME.
2023-12-19 | GSE211583 | GEO
Project description:Hepatic daily rhythms are coordinated by feeding and the molecular circadian clock, ensuring metabolic homeostasis. Disrupted feeding schedules promote circadian misalignment and metabolic diseases but the underlying mechanisms remain scarce. Post-translational modifications have emerged as key regulators of circadian metabolic outputs. Here, we show that the mitochondrial enzyme Acyl-CoA synthetase family member 3 (ACSF3) oscillates in phase with different feeding schedules to drive rhythmic lysine-malonylation and coordinate daily hepatic metabolism. Hepatic Acsf3 knockdown drastically affected lysine-malonylation rhythms, decreased fasting glycemia, insulin sensitivity and AKT phosphorylation indicative of perturbed glucose homeostasis. Concomitantly, Acsf3 knockdown shifted lipid oxidation from mitochondria to peroxisomes, enhanced lipogenesis and triglyceride synthesis, while increasing diurnal autophagy. Multi-omics profiling uncovered specific lysine-malonylation targets in glycolysis, the TCA cycle, fatty-acid oxidation and autophagy. Our findings uncover hepatic ACSF3 as a pivotal molecular nexus that integrates feeding time with dynamic protein lysine-malonylation and orchestrates the diurnal rhythm of liver metabolism.
2026-07-07 | GSE330452 | GEO
Project description:Virtually every mammalian tissue exhibits rhythmic expression in thousands of genes, which activate tissue-specific processes at appropriate times of the day. Much of this rhythmic expression is thought to be driven cell-autonomously by molecular circadian clocks present throughout the body. However, increasing evidence suggests that systemic signals, and more specifically rhythmic food intake (RFI), can regulate rhythmic gene expression independently of the circadian clock. To determine the relative contribution of cell autonomous clocks versus RFI in the regulation of rhythmic gene expression, we developed a system that allows long-term manipulation of the daily rhythm of food intake in the mouse, and analyzed liver gene expression by RNA-Seq in mice fed ad libitum, only at night, or arrhythmically (mouse eating 1/8th of their daily food intake every 3 hours). We show that 70% of the cycling mouse liver transcriptome loses rhythmicity under arrhythmic feeding. Remarkably, this loss of rhythmic gene expression under arrhythmic feeding is independent of the liver circadian clock, which continues to exhibit normal oscillations in core clock gene expression. Many genes that lose rhythmicity participate in the regulation of metabolic processes such as lipogenesis and glycogenesis, likely contributing to an increased sensitivity to insulin that was observed in arrhythmically-fed mice. We also show that night-restricted feeding significantly increases the number of rhythmically expressed genes as well as the amplitude of the rhythms. Together, these results indicate that metabolic transcription factors control a large fraction of the rhythmic mouse liver transcriptome, and demonstrate that systemic signals driven by rhythmic food intake play a more important role than the cell-autonomous circadian clock in driving rhythms in liver gene expression and metabolic functions.
2019-04-25 | GSE118967 | GEO