Effects of astrocytic absence of glucose transporter 1 (GLUT1) on the cortical astrocytic translatome
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ABSTRACT:
PROVIDER: PRJNA927282 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23217456.fastq.gz | Fastqsanger.gz | |||
| SRR23217457.fastq.gz | Fastqsanger.gz | |||
| SRR23217458.fastq.gz | Fastqsanger.gz | |||
| SRR23217459.fastq.gz | Fastqsanger.gz | |||
| SRR23217460.fastq.gz | Fastqsanger.gz |
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Project description:Brain activities rely on a steady supply of blood glucose, which is shuttled into the brain by glucose transporters and used to fuel metabolic pathways and energy demands in all neural cells. Astrocytes express glucose transporter 1 (GLUT1), which is considered the key glucose uptake route for glycolytic astrocytes to ensure their metabolic support functions to neurons and other glial cells in vivo. GLUT1 deficiency causes severe developmental impairments, however, the role of GLUT1 in astroglial glucose metabolism and brain function is poorly understood. Here we examine the effect of astrocytic GLUT1 deletion on the active translatome of astrocytes in the the mouse cortex.
2025-01-15 | GSE223687 | GEO
Project description:The Glucose transporter 1 (GLUT1) is one of the most abundant proteins within the erythrocyte membrane and is required for glucose and dehydroascorbic acid (Vitamin C precursor) transport. It is widely recognized as a key protein for red cell structure, function, and metabolism. Previous reports highlighted the importance of GLUT1 activity within these uniquely glycolysis-dependent cells, in particular for increasing antioxidant capacity needed to avoid irreversible damage from oxidative stress in humans. However, studies of glucose transporter roles in erythroid cells are complicated by species-specific differences between humans and mice. Here, using CRISPR mediated gene editing of immortalized erythroblasts and adult CD34 hematopoietic progenitor cells, we generate committed human erythroid cells completely deficient in expression of GLUT1. We show that absence of GLUT1 does not impede human erythroblast proliferation, differentiation, or enucleation. This work demonstrates for the first-time generation of enucleated human reticulocytes lacking GLUT1. The GLUT1-deficient reticulocytes possess no tangible alterations to membrane composition or deformability in reticulocytes. Metabolomic analyses of GLUT1-deficient reticulocytes reveal hallmarks of reduced glucose import, downregulated metabolic processes and upregulated AMPK-signaling, alongside alterations in antioxidant metabolism, resulting in increased osmotic fragility and metabolic shifts indicative of higher oxidant stress. Despite detectable metabolic changes in GLUT1 deficient reticulocytes, the absence of developmental phenotype, detectable proteomic compensation or impaired deformability comprehensively alters our understanding of the role of GLUT1 in red blood cell structure, function and metabolism. It also provides cell biological evidence supporting clinical consensus that reduced GLUT1 expression does not cause anemia in GLUT1 deficiency syndrome.
2024-02-29 | MSV000094204 | MassIVE
Project description:Effector (Teff) and regulatory (Treg) CD4 T cells undergo metabolic reprogramming to support proliferation and immune function. While Phosphatidylinositide 3-kinase (PI3K)/Akt/mTORC1 signaling induces the glucose transporter Glut1 and aerobic glycolysis for Teff proliferation and inflammatory function, mechanisms that regulate Treg metabolism and function remain unclear. We show that TLR signals that promote Treg proliferation increase Glut1, PI3K/Akt/mTORC1 signaling, and glycolysis. However, TLR-induced mTORC1 signaling also impaired Treg suppressive capacity. Conversely, FoxP3 opposed PI3K/Akt/mTOR signaling to reduce glycolysis and anabolic metabolism while increasing oxidative and catabolic metabolism. Importantly, Glut1 expression was sufficient to increase Treg numbers but reduced suppressive capacity and FoxP3 expression. Thus, inflammatory signals and FoxP3 balance mTORC1 signaling and glucose metabolism to control Treg proliferation and suppressive function.
2016-08-30 | GSE84919 | GEO
Project description:Hypothesis: Overexpression of the GLUT1 facilitative glucose transporter, in A7r5 vascular smooth muscle cells, is sufficient and/or necessary to induce alterations in gene expression which influence apoptosis, growth, and proliferation.
2009-10-23 | GSE15713 | GEO
Project description:Hypothesis: Overexpression of the GLUT1 facilitative glucose transporter, in A7r5 vascular smooth muscle cells, is sufficient and/or necessary to induce alterations in gene expression which influence apoptosis, growth, and proliferation. Experiment Overall Design: Scientific Approach: A7r5 rat embryonic vascular smooth muscle cells (VSMCs) (ATCC, CRL-1444) were infected for 72 hours with adenoviral vectors containing human GLUT1 or empty vector controls at a multiplicity of infection of 10 (MOI of 1 = 100 particles/cell) and grown in both high glucose (25mM) and low glucose (5.5mM) media. The human GLUT1 cDNA adenoviral vector and empty vector controls were a gift from Dr Arno Kumagai (University of Michigan). Total RNA was isolated using TRIzol (Invitrogen Life Technologies, Carlsbad, CA), followed by extraction with phenol/chloroform until the interface was clear. Total RNA was further purified using Qiagen RNeasy Mini Kit (Qiagen 74106). Immunoblot analysis was conducted to confirm GLUT1 overexpression at the time of Total RNA isolation (72 hours post-infection) for each condition. Experiment Overall Design: Number of chips: Total RNA was isolated from each of 2 conditions (control cells in low glucose (5.5mM), and GLUT1 overexpressing cells in low glucose), on three separate days and pooled to obtain one sample for each condition. In total we submitted two samples.
2009-11-07 | E-GEOD-15713 | biostudies-arrayexpress
Project description:Glucose is critical to the development, homeostasis, and survival of nucleus pulposus cells. GLUT1 is a major glucose transporter, a NP phenotypic cell marker, and highly expressed in nucleus pulposus (NP) cells, however its level of importance in NP cell development and homeostasis is unknown. We used microarrays to explore the transcriptomics of differentially expressed genes between wildtype and Glut1 cKO NP cells in 9-month-old mice.
2023-06-30 | GSE208396 | GEO
Project description:Macrophages (MΦs) are heterogeneous and metabolically flexible with metabolism strongly affecting immune activation. A classic response to pro-inflammatory activation is increased flux through glycolysis with a downregulation of oxidative metabolism, while alternative activation is primarily oxidative which begs the question of whether targeting glucose metabolism is a viable approach to control MΦ activation. We created a murine model of myeloid-specific glucose transporter GLUT1 (Slc2a1) deletion. Bone marrow derived MΦs (BMDM) from Slc2a1M-/- mice failed to uptake glucose and demonstrated reduced glycolysis and Pentose Phosphate Pathway activity. Activated BMDMs displayed elevated metabolism of oleate and glutamine, yet maximal respiratory capacity was blunted in MΦ lacking GLUT1 demonstrating an incomplete metabolic reprogramming. Slc2a1M-/- BMDMs displayed a mixed inflammatory phenotype with reductions of the classically-activated pro- and anti-inflammatory markers, yet less oxidative stress. Slc2a1M-/- BMDMs had reduced pro-inflammatory metabolites, whereas metabolites indicative of alternative activation - such as ornithine and polyamines - were greatly elevated in the absence of GLUT1. Adipose tissue MΦs of lean Slc2a1M-/- mice had increased alternative M2-like activation marker mannose receptor CD206, yet lack of GLUT1 was not a critical mediator in the development of obesity-associated metabolic dysregulation. However, Ldlr-/- mice lacking myeloid GLUT1 developed unstable atherosclerotic lesions. Defective phagocytic capacity in Slc2a1M-/- BMDMs may have contributed to unstable atheroma formation. Together our findings suggest that while lack of GLUT1 blunted glycolysis and PPP, MΦ were metabolically flexible enough that inflammatory cytokine release was not dramatically regulated yet phagocytic defects hindered MΦ function in chronic diseases. Control mice are noted as WT or Slc2a1 fl/fl and myeloid GLUT1 deficient are KO or Slc2a1M-/- (LysMCre X Slc2a1fl/fl) for myeloid deficiency.
2019-02-13 | GSE123289 | GEO
Project description:The tumor microenvironment presents many obstacles to effective CAR T cell therapy, including glucose competition from tumor and myeloid cells. Using mouse models of acute lymphoblastic leukemia (ALL), renal cell carcinoma (RCC), and glioblastoma (GBM), we show that enforced expression of the glucose transporter GLUT1 enhances anti-tumor efficacy and promotes favorable CAR T cell phenotypes for two clinically relevant CAR designs, 19-28z and IL13Ra2-BBz. In the NALM6 ALL model, 19-28z-GLUT1 promotes Tscm formation and prolongs survival. RNA sequencing of these CAR T cells reveals that overexpression of GLUT1, but not GLUT3, enriches for genes involved in glycolysis, mitochondrial respiration, and memory precursor phenotypes. Extending these data, 19-28z-GLUT1 CAR T cells improve tumor control and response to rechallenge in an RCC patient derived xenograft model. Furthermore, IL13Ra2-BBz CAR T cells overexpressing GLUT1 prolong survival of mice bearing orthotopic GBMs and exhibit decreased exhaustion markers. This novel engineering approach can offer a competitive advantage to CAR T cells in harsh tumor environments where glucose is limiting.
2024-05-30 | GSE265904 | GEO
Project description:Breast cancer (BC) is a commonly identified life-threatening type of cancer and a major cause of death among women worldwide. Several microRNAs (miRs), including miR-143-5p, have been reported to be vital for regulating hallmarks of cancer; however, the effect of miR-143-5p on BC requires further exploration. The present study performed bioinformatics analysis on GSE42072 and GSE41922 datasets from the National Center for Biotechnology Information Gene Expression Omnibus (GEO) database to identify miR-143-5p expression patterns. Furthermore, miR-143-5p expression was detected in BC cell lines and tissues via reverse transcription-quantitative PCR. Post-transfection with miR-143-5p mimics, Cell Counting Kit-8, colony formation and Transwell assays were performed to explore the effects of miR-143-5p on BC cell proliferation, colony formation, and migration. The association of miR-143-5p with the hypoxia-inducible factor-1α (HIF-1α)-associated glucose transporter 1 (GLUT1) pathway was explored via western blotting, immunofluorescence and dual-luciferase reporter assay. The present study detected high expression of miR-143-5p in BC tissue of the GSE42072 and serum of the GSE41922 datasets by GEO chip analysis. Additionally, the expression levels of miR-143-5p were decreased in BC tissues compared with those in adjacent healthy tissues, and low miR-143-5p expression was associated with a poorer prognosis and shorter survival time in patients with BC. In vitro, miR-143-5p expression levels were decreased in BC cells, and transfection with miR-143-5p mimics suppressed BC cell proliferation, colony formation, migration. Furthermore, miR-143-5p targeted the HIF-1α-related GLUT1 pathway, and inhibited HIF-1α and GLUT1 expression. Additionally, HIF-1α agonists reversed the miR-143-5p-induced inhibition during tumorigenesis. In conclusion, miR-143-5p exhibited low expression in BC tissues, and suppressed BC cell proliferation, colony formation, migration. Moreover, the antitumor effects of miR-143-5p targeted the HIF-1α-related GLUT1 pathway.
2022-02-26 | E-MTAB-11160 | biostudies-arrayexpress
Project description:Glucose uptake increases during B cell activation and plasma cell differentiation. However, conflicting findings regarding the role of glucose at different stages of B cell activation prevents establishing a clear metabolic profile. To determine whether glucose is required for establishing humoral immunity, we deleted the glucose transporter type 1 (GLUT1)-encoding gene (Slc2a1fl/fl) in mature B cells by CD23-mediated Cre expression (GLUT1-cKO). While B cell development was normal, germinal center B cell and antibody-secreting cell numbers (ASCs) were severely reduced in GLUT1-cKO mice. In addition, these mice could hardly mount antigen-specific antibody titers after vaccination. Activation of GLUT1-deficient B cells in vitro was impaired and the remaining plasmablasts abolished glycolysis, relying on mitochondrial activity and fatty acid metabolism. Metabolomics combined with genome-wide transcriptome analysis revealed a dramatically altered anaplerotic balance in GLUT1-deficient ASCs. Although the cells attempt to compensate for glucose deprivation by increasing their mitochondrial mass and the expression of genes responsible for glycolysis, the tricarboxylic acid cycle and the hexosamine synthesis pathways, they lack both the necessary metabolites for energy production and functional mitochondrial respiration. Consequently, protein synthesis was limited in GLUT1-deficient ASCs. Thus, we identified GLUT1 as a critical metabolic player defining the germinal center response and humoral immunity.
2024-02-09 | GSE230073 | GEO