Gene expression profile at single cell level of GFP labeled islet β cells from streptozotocin (STZ) treated Ins/β-lineage-labeled mice
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ORGANISM(S): Mus musculus
PROVIDER: GSE203042 | GEO | 2023/05/01
REPOSITORIES: GEO
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Project description:Gene expression profile at single cell level of GFP labeled islet β cells from streptozotocin (STZ) treated Ins/β-lineage-labeled mice
| PRJNA838229 | ENA
Project description:Objectives The streptozotocin (STZ) model is widely used in diabetes research. However, the cellular and molecular states of pancreatic endocrine cells in this model remain unclear. This study explored the molecular characteristics of islet cells treated with STZ and re-evaluated β-cell dysfunction and regeneration in the STZ model. Methods We performed single-cell RNA sequencing of pancreatic endocrine cells from STZ-treated mice. High-quality sequencing data from 2,999 cells were used to identify clusters via Louvain clustering analysis. Principal component analysis (PCA), t-distributed stochastic neighbor embedding (t-SNE), uniform manifold approximation and projection (UMAP), force-directed layout (FDL), and differential expression analysis were used to define the heterogeneity and transcriptomic changes in islet cells. In addition, qPCR and immunofluorescence staining were used to confirm findings from the sequencing data. Results Untreated β-cells were divided into two populations at the transcriptomic level, a large high-Glut2 expression (Glut2high) population and a small low-Glut2 expression (Glut2low) population. At the transcriptomic level, Glut2low β-cells in adult mice did not represent a developmentally immature state, although a fraction of genes associated with β-cell maturation and function were downregulated in Glut2low cells. After a single high-dose STZ treatment, most Glut2high cells were killed, but Glut2low cells survived and over time changed to a distinct cell state. We did not observe conversion of Glut2low to Glut2high β-cells up to 9 months after STZ treatment. In addition, we did not detect transcriptomic changes in the non-β endocrine cells or a direct trans-differentiation pathway from the α-cell lineage to the β-cell lineage in the STZ model. Conclusions We identified the heterogeneity of β-cells in both physiological and pathological conditions. However, we did not observe conversion of Glut2low to Glut2high β-cells, transcriptomic changes in the non-β endocrine cells, or direct trans-differentiation from the α-cell lineage to the β-cell lineage in the STZ model. Our results clearly define the states of islet cells treated with STZ and allow us to re-evaluate the STZ model widely used in diabetes studies.
2020-04-23 | GSE137909 | GEO
Project description:Streptozotocin (STZ) is an anti-cancer drug that is primarily used to treat neuroendocrine tumors (NETs) in clinical settings and develop type 1 diabetes rodent models in experimental fields. STZ is incorporated into cells through the glucose transporter, GLUT2, which is primarily expressed in pancreatic β-cells or proximal tubular epithelial cells in the kidney. However, its cytotoxic effects on kidney cells have been underestimated and the underlying mechanisms remain unclear. We herein demonstrated that DNA damage and subsequent p53 signaling were responsible for the development of STZ-induced tubular epithelial injury. We detected tubular epithelial DNA damage in NET patients treated with STZ. Unbiased transcriptomics of tubular epithelial cells in vitro showed the activation of the p53 signaling pathway by STZ. STZ induced DNA damage and activated p53 signaling in vivo in a dose-dependent manner, resulting in reduced membrane transport. The localization of STZ-induced kidney injury was limited to within the kidney cortex, which was independent of blood glucose. The pharmacological inhibition of p53 and sodium-glucose transporter 2 (SGLT2) mitigated STZ-induced epithelial injury. However, the cytotoxic effects of STZ on pancreatic β-cells were preserved in SGLT2 inhibitor-treated mice. The present results demonstrate the strong proximal tubular-specific cytotoxicity of STZ and the underlying mechanisms in vivo, which may be ameliorated by a SGLT2 inhibitor pretreatment. Since the cytotoxic effects of STZ against β-cells were not impaired by dapagliflozin, a pretreatment with a SGLT2 inhibitor has potential as a preventative remedy for kidney injury in NET patients treated with STZ.
2023-06-07 | GSE215337 | GEO
Project description:Background and Aims: It is well demonstrated that in the beta cell population of the pancreas there is a dynamic turnover, which results from the net balance of several processes; beta cell replication, apoptosis and neogenesis. These processes have been studied in partial pancreatectomy and glucagon-like peptide 1 treated animals, where an increase in pancreas regeneration has been observed. Similarly, sodium tungstate, which decreases hyperglycemia in several animal models of diabetes, promotes a rise in the beta cell mass of nSTZ and STZ animals. However, the molecular mechanisms underlying this pancreas regeneration remain unknown. Therefore the objective of this study is to identify which genes are up or down regulated in the increase of the beta cell population of STZ rats treated with sodium tungstate. Materials and methods: Adult male Wistar (225-250 g) rats were kept under a constant 12-hour light-dark cycle and rats were kept under a constant 12-hour light-dark cycle and were allowed to eat and drink freely. Diabetes was induced by a single i.p. injection of streptozotocin (STZ) (70 mg/Kg body weight) in 0.9% NaCl with 100 mmol/L sodium citrate buffer (pH 4.5). Diabetes was confirmed by determination of its hyperglycaemia (>500mg/dL [Reflotron, Roche Diagnostic]). Healthy rats received an i.p. injection of the vehicle. Treatment started 7 days after the STZ or vehicle injection. Diabetic and healthy rats were divided into two groups. In the first (untreated), rats received deionized drinking water; in the second (treated) group, they were given a solution of sodium tungstate. During the first week of treatment, the rats received a solution of 0.7 mg/mL and in the next 4-5 weeks, the concentration was increased to 2 mg/mL. At the end of the experiment, the animals were sacrificed and pancreatic RNA isolated. Three chips (Affymetrix RAE-230A) were hybridized for each of the four experimental groups (untreated and treated healthy rats and untreated and treated diabetic rats). The raw intensity data obtained from the microarrays was normalized and summarized using the Bioconductor package RMA. Keywords = pancreas regeneration Keywords = STZ Keywords = diabetes Keywords = tungstate Keywords = insulin-like agents Keywords = beta cell plasticity Keywords = neogenesis Keywords: ordered
2006-04-01 | GSE2470 | GEO
Project description:Mulberry leaf ameliorate STZ induced diabetic rat by regulating hepatic glycometabolism and fatty acid β-oxidation
2024-10-29 | PXD057279 |
Project description:The chronic inflammation resultant from type 2 diabetes (T2D) is also associated with spinal pathologies, including intervertebral disc (IVD) degeneration and chronic neck and back pain. Although confounding factors, such as increased weight gain in obesity, studies have shown that even after adjusting age, body mass index, and genetics (e.g. twins), patients with T2D suffer from disproportionately more IVD degeneration and back pain. We hypothesize that chronic T2D fosters a proinflammatory microenvironment within the IVD that promotes degeneration and disrupts disc homeostasis. To test this hypothesis, we evaluated two commonly used mouse models of T2D – the leptin-receptor deficient mouse (db/db) and the chronic high-fat diet in mice with impaired beta-cell function (STZ-HFD). STZ-HFD IVDs were more degenerated and showed differential expression of chemokines from the db/db models. Moreover, the RNAseq analysis revealed vast transcriptional dysregulation of many pathways in the STZ-HFD but not in the db/db tissues. Taken together, the STZ-HFD may better recapitulates the complexities of the chronic inflammatory processes in the IVD during T2D
2025-03-25 | GSE288503 | GEO
Project description:The experiment was designed to obtain a broader unbiased view of the changes in islet macrophages following low dose STZ challenge. Mice were purchased from Jackson Laboratory (Bar Harbor, ME). 16-20-week-old C57BL/6J males were given 30 mg/kg STZ or acetate buffer (control) i.p. (intraperitoneal injection) for 5 consecutive days. Following the first STZ or buffer injection mice were sacrificed on day 14 and islets were isolated by collagenase digestion. Freshly isolated islets were dispersed in 0.02% Trypsin-EDTA for 3 minutes followed by up to 1 minute of pipetting under a stereomicroscope to obtain a single cell solution. Islet media was added to stop the reaction. Islets from 10 mice were pooled per sample (N). Dispersed islets were washed with FACS buffer (1% heat inactivated FBS, 1 mM EDTA, 11 mM glucose in PBS). Cells were kept on ice and pre-incubated with Fc Block (1:100) for 5 minutes, followed by 30 min incubation with CD45-eFluor 450 (1:250; clone 30-F11), Ly-6C-APC (1:1,200; clone HK1.4), CD11b-PE (1:1,200; clone M1/700, F4/80-FITC (1:150; clone BM8), CD11c-PECy7 (1:150; clone N418), and the viability dye 7AAD (1:2,000). Unstained, single stains, and fluorescence minus one controls were used for setting gates and compensation. Viable, single CD45+Ly6c-Cd11b+Cd11c+F4/80+ cells were sorted using a BD FACS Aria IIu directly into lysis buffer, and the RNeasy Plus Micro Kit from Qiagen was used to isolate total RNA. Total RNA quality control quantification was performed using an Agilent 2100 Bioanalyzer. All RNA samples had an RNA integrity number (RIN) ≥9.1. The NeoPrep Library Prep System from Ilumina was used for library preparation followed by sequencing using standard Illumina methods and Ilumina NextSeq500.
2019-11-01 | E-MTAB-7234 | biostudies-arrayexpress
Project description:Chemicals, such as MNU (N-methyl-N-nitrosourea) and NaIO3 (sodium iodate), are widely used to induce retinal degeneration in rodents. Streptozotocin (STZ) is an analog of N-acetyl glucosamine in which an MNU moiety is linked to a hexose and has a special toxic effect on insulin-producing pancreatic β-cells. It is commonly used to induce hyperglycemia to model diabetes. While intracerebroventricular injection of STZ can produce Alzheimer's disease independent of hyperglycemia, most retinal studies using STZ focus on the effects of hyperglycemia on the retina, but whether STZ has any impact on retinal cells independent of hyperglycemia is unknown. We aimed to investigate the role of cytotoxicity of STZ in rat retina. Intravitreal (5ug or 10ug) or subcutaneous (30mg/kg) injection of STZ at the early stage of newborn rats couldn’t induce hyperglycemia but caused NSIR (neonatal STZ-induced retinopathy), including reduced ERG amplitudes, retinal rosettes and apoptosis, cell cycle arrest, microglial activation, and delayed retinal angiogenesis. STZ did not affect the early-born retinal cell types but significantly reduced the late-born ones. Short-term and long-term hyperglycemia had no significant effects on the NSIR phenotypes. RNA sequencing revealed that STZ induces oxidative stress and activates the p53 pathway of retinal cells. Locally or systemically, STZ injection after P8 couldn’t induce NSIR when all retinal progenitors exit the cell cycle. Thus, NSIR in rats is independent of hyperglycemia but due to STZ’s direct cytotoxic effects on retinal progenitor cells. NSIR is a typical reaction to STZ-induced retinal oxidative stress and DNA damage. This significant finding suggests that NSIR may be a valuable model for studying retinal progenitor DNA damage-related diseases, potentially leading to new insights and treatments.
2024-07-16 | GSE272311 | GEO
Project description:The effect of liraglutide on the kidney proteome in the STZ mouse model compared to healthy and STZ diabetic control groups.
2019-01-18 | PXD003007 | Pride
Project description:Alzheimer’s Disease (AD) is an age-related neurodegenerative disorder characterized by progres-sive memory loss and cognitive impairment, affecting 35 million individuals worldwide. Intracer-ebroventricular (ICV) injection of low to moderate doses of STZ in adult male Wistar rats can re-produce classical physiopathological hallmarks of AD. This biological model is known as ICV-STZ. Most studies are focused on the description of behavioral and morphological aspects of the ICV-STZ model. However, the knowledge regarding the molecular aspects of the ICV-STZ model is still in-cipient. Therefore, this work is a first attempt to provide a wide proteome description of the ICV-STZ model based on Mass spectrometry (MS). To achieve that, samples from pre-frontal cortex (PFC) and hippocampus (HPC) of the ICV-STZ model and control (wild-type) were used. Differ-ential protein abundance, pathway, and network analysis was performed based on the protein identification and quantification of the samples. Our analysis revealed dysregulated biological pathways implicated in early stages of Late-Onset Alzheimer’s Disease (LOAD) based on differen-tially abundant proteins (DAPs). Some of these DAPs had their mRNA expression further inves-tigated through qRT-PCR. Our results shed light on the AD onset and demonstrate the ICV-STZ as a valid model for LOAD proteome description.
2024-06-22 | PXD048720 | Pride