Single-cell RNA sequencing of pancreatic islets from obese mice with different diabetes risk reveals diabetes-susceptible β cell clusters
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE159211 | GEO | 2022/07/07
REPOSITORIES: GEO
Similar Datasets
Project description:Mouse strains like NZO and B6-ob/ob differ in their susceptibility to diet-induced diabetes. Comparison of the islet transcriptomes already revealed different biological processes, here we focused on alternative splicing events as one possible mechanism.
2021-09-04 | GSE183247 | GEO
Project description:Mouse strains like NZO and B6-ob/ob differ in their susceptibility to diet-induced diabetes. Comparison of the islet transcriptomes leads to genes that are either involved in protection or apoptosis of pancreatic islet cells upon carbohydrate challenge. Genes being upregulated in NZO can be seen as drivers of beta cell failure, while genes upregulated in B6-ob/ob are most likely involved in beta cell protection.
2018-02-19 | GSE64956 | GEO
Project description:Young and aged, diabetes-prone (NZO/HIBomDife) as well as diabetes-resistant (B6.V-Lep ob/ob) mice exhibited different islet functions and phenotypes in response to a carbohydrate-rich diet (CRD) subsequent to a high-fat, carbohydrate-free diet (HFD). To unravel the molecular basis underlying these alterations, a microarray-based transcriptome analysis of isolated pancreatic islets before and after 2 days of CRD feeding was performed. A high number of differentially expressed genes associated with redox homeostasis, in particular Thioredoxin-interacting protein (Txnip), as well as genes involved in cell cycle entry and cell proliferation, such as cyclins, cyclin-dependent kinases and Mki67 were identified and associated with these changes. In addition, aged NZO/HIBomDife and age-matched, B6.V-Lep ob/ob mice revealed a high overlap of regulated genes, also linked to cell cycle progression under the same dietary regimen.
2023-11-03 | GSE160694 | GEO
Project description:Overnutrition contributes to insulin resistance, obesity and metabolic stress, initiating a loss of functional beta-cells and diabetes development. Whether these damaging effects are amplified in advanced age is barely investigated. Therefore, New Zealand Obese (NZO) mice, a well-established model for the investigation of human obesity-associated type 2 diabetes, were fed a metabolically challenging diet with a high-fat, carbohydrate restricted period followed by a carbohydrate intervention in young as well as advanced age. Interestingly, while young NZO mice developed massive hyperglycemia in response to carbohydrate feeding, leading to beta-cell dysfunction and cell death, aged counterparts compensated the increased insulin demand by persistent beta-cell function and beta-cell mass expansion. Beta-cell loss in young NZO islets was linked to increased expression of thioredoxin-interacting protein (TXNIP), presumably initiating an apoptosis-signaling cascade via caspase-3 activation. In contrast, islets of aged NZOs exhibited a sustained redox balance without changes in TXNIP expression, associated with higher proliferative potential by cell cycle activation. These findings support the relevance of a maintained proliferative potential and redox homeostasis for preserving islet functionality under metabolic stress, with the peculiarity that this adaptive response emerged with advanced age in diabetes-prone NZO mice.
2020-11-02 | GSE150281 | GEO
Project description:We report the high-throughput miRNA sequencing of isolated colonic and jejunal Kit+ interstitial cells of Cajal (ICC) from Lepob/ob;KitcopGFP mice, which develop type 2 diabetes, and Lepob/+;KitcopGFP mice which are non-diabetic counterparts and control
2020-12-31 | GSE139578 | GEO
Project description:Gene expression in diabetes-prone (NZO/HiBomDife) and diabetes-resistant (C57BL/6.V-Lepob/ob) mouse strains
| PRJNA272583 | ENA
Project description:Obesity is associated with impairments of wound healing and tissue regeneration. Angiogenesis, the formation of new blood capillaries, plays a key role in organ regeneration and repair. Inhibition of lung angiogenesis impairs regenerative lung growth after unilateral pneumonectomy (PNX). However, the effects of obesity on post-PNX lung vascular and alveolar morphogenesis remain unclear. In this report, we have demonstrated that regenerative lung growth and angiogenic factor VEGFA expression induced by PNX are inhibited in Lepob/ob obese mice compared to Lepob/- mice. The levels of adiponectin, one of the adipokines that exhibits pro-angiogenic and vascular protective properties, increase in endothelial cells (ECs) isolated from remaining mouse lungs after unilateral PNX, while these effects are attenuated in Lepob/ob obese mice. Post-PNX lung growth, vascular and alveolar morphogenesis, and VEGFA levels in the lungs are inhibited in adiponectin knockout mice. Adiponectin agonist, AdipoRon stimulates post-PNX lung growth and vascular and alveolar morphogenesis in Lepob/ob obese mice. These findings suggest that obesity impairs lung vascular and alveolar regeneration and adiponectin may be one of the key molecules to improve lung regeneration in obese people.
2024-11-06 | GSE179227 | GEO
Project description:Diabetes-resistant and diabetes-prone female New Zealand Obese mice were classified based on liver fat content and early blood glucose concentrations at 10 weeks of age before the onset of T2D. By using transcriptome and DNA methylome analysis of Langerhans islets, we identified early epigenetic alteration in mice and humans which could serve as putative epigenetic biomarkers
2020-10-28 | GSE143875 | GEO
Project description:Genetic and lifestyle factors greatly impact the development of metabolic diseases including Type 2 Diabetes (T2D). It is an ongoing challenge to determine how these factors and their interplay specifically contribute to risk of T2D. Mouse models allow precise control of environment and genetic replication, and mouse strains fed an unhealthy diet show variable signs of metabolic dysfunction ranging from overt diabetes to diet-induced obesity to complete resistance. When fed a high-fat high-sugar (HFHS) diet, NZO/HlLtJ (NZO) mice become severely obese and many become diabetic, C57BL/6J (B6J) mice develop obesity but seldom overt diabetes, and CAST/EiJ (CAST) mice are resistant to obesity and glucose intolerance. We present deep molecular and metabolic profiling of these three genetically diverse mouse strains fed control (low fat, no sugar) and HFHS diets to define inherited aspects of metabolism that may impact diabetes risk. Transcriptomic analysis of eight tissues revealed significant tissue-specific molecular variability underpinning the metabolic differences across strains. The most distinct diet responses were observed in adipose and pancreas. In adipose tissue, differences in immunometabolism, lipid metabolism, and oxidative phosphorylation pathways parallel the susceptibility to obesity and diabetes across strains. In pancreatic islets, there was inflammation associated with HFHS diet in NZO mice that is expected to contribute to beta cell dysfunction. Taken together, physiological and molecular profiling of these genetically diverse mouse strains provides a foundation for deeper understanding the molecular basis of individual differences in susceptibility to metabolic diseases.
2023-12-31 | GSE234956 | GEO
Project description:Dysfunctional islets of Langerhans are a hallmark of type 2 diabetes (T2D). We hypothesize that differences in islet gene expression alternative splicing which can contribute to altered protein function also participate in islet dysfunction. RNA sequencing (RNAseq) data from islets of obese diabetes-resistant and diabetes-susceptible mice were analyzed for alternative splicing and its putative genetic and epigenetic modulators. We focused on the expression levels of chromatin modifiers and SNPs in regulatory sequences. We identified alternative splicing events in islets of diabetes-susceptible mice amongst others in genes linked to insulin secretion, endocytosis or ubiquitin-mediated proteolysis pathways. The expression pattern of 54 histones and chromatin modifiers, which may modulate splicing, were markedly downregulated in islets of diabetic animals. Furthermore, diabetes-susceptible mice carry SNPs in RNA-binding protein motifs and in splice sites potentially responsible for alternative splicing events. They also exhibit a larger exon skipping rate, e.g., in the diabetes gene Abcc8, which might affect protein function. Expression of the neuronal splicing factor Srrm4 which mediates inclusion of microexons in mRNA transcripts was markedly lower in islets of diabetes-prone compared to diabetes-resistant mice, correlating with a preferential skipping of SRRM4 target exons. The repression of Srrm4 expression is presumably mediated via a higher expression of miR-326-3p and miR-3547-3p in islets of diabetic mice. Thus, our study suggests that an altered splicing pattern in islets of diabetes-susceptible mice may contribute to an elevated T2D risk.
| S-EPMC8395343 | biostudies-literature