Stat1-induced NAMPT sustains glycolysis to regulate gene expression in classically activated macrophages
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA560187 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9965206.fastq.gz | Fastqsanger.gz | |||
| SRR9965207.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 2 of 2 |
Similar Datasets
Project description:Stat1-induced NAMPT sustains NAD levels to regulate gene expression in classically activated macrophages
| PRJNA509925 | ENA
Project description:Single Cell RNA Sequencing is used to profile in vivo responses by immune cells lacking the Nampt NRE1 region to melanoma challenge, finding multiple defects in macrophages and other myeloid APCs. We analyzed B16F10 melanoma tumor infiltrating immune cells from mice specifically lacking NRE1 in hematopoietic cells, finding inflammatory and metabolic defects in APC populations within tumors, correlating with trends toward defective control of malignant growth.
2019-10-01 | GSE135814 | GEO
Project description:We identify gene regulation patterns that influence inflammation and metabolism during interferon treatment in the presence of NAD salvage synthesis inhibitors and products
2019-04-30 | GSE123822 | GEO
Project description:Neural stem/progenitor cell (NSPC) proliferation and self-renewal, as well as insult-induced differentiation, decrease markedly with age, but the molecular mechanisms responsible for these declines remain unclear. Here we show that levels of NAD+ and nicotinamide phosphoribosyltransferase (Nampt), the rate-limiting enzyme in mammalian NAD+ biosynthesis, decrease with age in the hippocampus. Ablation of Nampt in adult NSPCs reduced their pool and proliferation in vivo. The decrease in the NSPC pool during aging can be rescued by enhancing hippocampal NAD+ levels. Nampt is the main source of NSPC NAD+ levels and required for G1/S progression of the NSPC cell cycle. Nampt is also critical for oligodendrocytic lineage fate decisions through a mechanism mediated redundantly by Sirt1 and Sirt2. Ablation of Nampt in the adult NSPCs in vivo reduced NSPC-mediated oligodendrogenesis upon injury. These phenotypes recapitulate defects in NSPCs during aging, implicating Nampt-mediated NAD+ biosynthesis as a mediator of these age-associated functional declines. Total RNA obtained from neurospheres derived from postnatal hippocampi subjected to 48 hours in vitro of incubation with Nampt-specific inhibitor FK866 (10 nM, 4 samples) or vehicle (DMSO, 1:1000, 4 samples).
2014-05-08 | E-GEOD-49784 | biostudies-arrayexpress
Project description:NAMPT is an enzyme in the mammalian NAD+ salvage pathway. Expression microarray analysis was used to study the effect of NAMPT knockdown on gene expression in MCF-7 breast cancer cells. Experiment Overall Design: Stable knockdown of NAMPT was achieved using a retroviral shRNA construct. An shRNA directed against Luciferase was used to generate the Luc control cells. Three independent biological replicates with matching Luc controls were analyzed using Affymetrix U133 A2.0 microarrays.
2009-06-08 | E-GEOD-13449 | biostudies-arrayexpress
Project description:Hypothesis is that NAMPT overexpression alters liver transcriptomics in genetically diabetic, obese db/db mice. We treated db/db mice n = 4 with adenovirus encoding GFP or NAMPT by tail-vein delivery.
2022-08-01 | E-MTAB-10984 | biostudies-arrayexpress
Project description:NAMPT is an enzyme in the mammalian NAD+ salvage pathway. Expression microarray analysis was used to study the effect of NAMPT knockdown on gene expression in MCF-7 breast cancer cells.
2009-05-28 | GSE13449 | GEO
Project description:Background: Signal Transducer and Activator of Transcription 1 (STAT1) has traditionally been regarded as a transmitter of interferon signaling and a pro-apoptotic tumor suppressor. Recent data have identified new functions of STAT1 associated with tumorigenesis and resistance to genotoxic stress, including ionizing radiation (IR) and chemotherapy. To investigate the mechanisms contributing to the tumorigenic functions of STAT1, we performed a combined transcriptomic-proteomic expressional analysis and found that STAT1 is associated with regulation of energy metabolism. Methods: We generated a stable knockdown of STAT1 in the SCC61 human squamous cell carcinoma cell line, established tumor xenografts in athymic mice, and compared transcriptomic and proteomic profiles of STAT1 wild-type (WT) and knockdown (KD) untreated or irradiated (IR) tumors. Transcriptional profiling was based on Affymetrix Human GeneChip® Gene 1.0 ST microarrays. Proteomes were determined from the MS/MS data by searching against the human subset of the UniProt database. Data were analyzed using Significance Analysis of Microarrays (SAM) for RNA and Visualize software for proteins. Functional analysis was performed with Ingenuity Pathway Analysis (IPA) with statistical significance measured by Fisher’s exact test. Results: Knockdown of STAT1 led to significant growth suppression in untreated tumors and radiosensitization of irradiated tumors. These changes were accompanied by alterations in the expression of genes and proteins of glycolysis (GG), the citrate cycle (CC) and oxidative phosphorylation (OP). Of these pathways, GG had the most concordant changes in gene and protein expression and demonstrated a STAT1-dependent expression of genes and proteins consistent with tumor-specific glycolysis. IR drastically suppressed the GG pathway in STAT1 KD tumors without significant change in STAT1 WT tumors. The STAT1 and glycolytic pathways were co-expressed in human breast tumors, and expression of STAT1-linked glycolytic genes was highly predictive of poor prognosis. Conclusions: Our results identify a previously uncharacterized function of STAT1 in tumors: expressional regulation of genes and enzymes involved in glycolysis, the citrate cycle, and mitochondrial oxidative phosphorylation, with predominant regulation of glycolysis. STAT1-dependent transcriptional and translational regulation of glycolysis suggests a potential role for STAT1 as a transcriptional modulator of genes responsible for the Warburg effect.
2009-04-28 | GSE15845 | GEO
Project description:Neural stem/progenitor cell (NSPC) proliferation and self-renewal, as well as insult-induced differentiation, decrease markedly with age, but the molecular mechanisms responsible for these declines remain unclear. Here we show that levels of NAD+ and nicotinamide phosphoribosyltransferase (Nampt), the rate-limiting enzyme in mammalian NAD+ biosynthesis, decrease with age in the hippocampus. Ablation of Nampt in adult NSPCs reduced their pool and proliferation in vivo. The decrease in the NSPC pool during aging can be rescued by enhancing hippocampal NAD+ levels. Nampt is the main source of NSPC NAD+ levels and required for G1/S progression of the NSPC cell cycle. Nampt is also critical for oligodendrocytic lineage fate decisions through a mechanism mediated redundantly by Sirt1 and Sirt2. Ablation of Nampt in the adult NSPCs in vivo reduced NSPC-mediated oligodendrogenesis upon injury. These phenotypes recapitulate defects in NSPCs during aging, implicating Nampt-mediated NAD+ biosynthesis as a mediator of these age-associated functional declines.
2014-05-08 | GSE49784 | GEO
Project description:Molecular clocks in the periphery coordinate tissue-specific daily biorhythms by integrating input from the hypothalamic master clock and intracellular metabolic signals. One such key metabolic signal is the cellular concentration of NAD+, which oscillates along with its biosynthetic enzyme, nicotinamide phosphoribosyltransferase (NAMPT). NAD+ levels feed back into the clock to influence rhythmicity of biological functions, yet whether this metabolic fine-tuning occurs ubiquitously across cell types and is a core clock feature is unknown. Here we show that NAMPT-dependent control over the molecular clock varies substantially between tissues. Brown adipose tissue (BAT) requires NAMPT to sustain the amplitude of the core clock, whereas rhythmicity in white adipose tissue (WAT) is only moderately dependent on NAD+ biosynthesis and the skeletal muscle clock is completely refractory to loss of NAMPT. In BAT and WAT, NAMPT differentially orchestrates oscillation of clock-controlled gene networks and the diurnality of metabolite levels. NAMPT coordinates the rhythmicity of TCA cycle intermediates in BAT, but not WAT, and loss of NAD+ abolishes these oscillations similarly to high fat diet (HFD)-induced circadian disruption. Adipose NAMPT depletion also improved the ability of animals to defend body temperature during cold stress but this is independent of time-of-day. Thus, our findings reveal that peripheral molecular clocks and metabolic biorhythms are shaped in a highly tissue-specific manner by NAMPT-dependent NAD+ synthesis.
2023-04-11 | GSE221550 | GEO