Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA214888 | ENA |
REPOSITORIES: ENA
Similar Datasets
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: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:We employed bulk RNA sequencing using the UCLA Technology Center for Genomics &Bioinformatics platform to investigate the role of nicotinamide phosphoribosyltransferase (NAMPT), a key enzyme in NAD+ biosynthesis, in AT2 cells in the lung. NAMPT has been implicated in regulating stem cell function, mitochondrial bioenergetics, apoptosis, and senescence in neurodegenerative diseases, endothelial cells, and human iPS cells. We used CRISPR/Cas9 system to knockout or activate NAMPT in immortalized IPF AT2 cells.
2026-03-30 | GSE295740 | GEO
Project description:We evaluated the effects of NAMPT (nicotinamide phosphoribosyltransferase) knockout on transcriptome in brown adipose tissue (BAT) by analyzing BAT obtained from control (Nampt-flox/flox, F1-F4) and adipocyte-specific Nampt knockout (ANKO, A1-A4) mice.
2019-11-14 | GSE137149 | GEO
Project description:We employed single-cell RNA sequencing using the 10x Genomics platform to investigate the role of nicotinamide phosphoribosyltransferase (NAMPT), a key enzyme in NAD+ biosynthesis, in AT2 cells in the lung. NAMPT has been implicated in regulating stem cell function, mitochondrial bioenergetics, apoptosis, and senescence in neurodegenerative diseases, endothelial cells, and human iPS cells. Single-cell lung suspensions were prepared from Nampt AT2 conditional knockout and control mice at day 0 and day 4 post-bleomycin injury. scRNA-seq was performed on FACS-sorted Epcam+ and CD45+ live cells, and purified cells were clustered to evaluate NAMPT function in AT2 and immune cells.
2026-03-30 | GSE295739 | GEO
Project description:We investigated the plasma and liver proteome changes in liver fibrosis in mice induced by hepatocyte-specific knockout of nicotinamide phosphoribosyltransferase (Nampt) upon a low-methionine, choline-free 60% high-fat (MCD) diet at multiple time points. We also investigated whether supplementation with nicotinamide riboside could alleviate liver injury and how the liver proteome changes upon NR supplementation.
2021-11-04 | PXD017170 | Pride
Project description:Type 2 diabetes (T2D) has become an epidemic in our modern lifestyle, likely due to calorie-rich diets overwhelming our adaptive metabolic pathways. One such pathway is mediated by nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in mammalian NAD+ biosynthesis, and the NAD+-dependent protein deacetylase SIRT1. Here we show that NAMPT-mediated NAD+ biosynthesis is severely compromised in metabolic organs by high-fat diet (HFD). Strikingly, nicotinamide mononucleotide (NMN), a product of the NAMPT reaction and a key NAD+ intermediate, ameliorates glucose intolerance by restoring NAD+ levels in HFD-induced T2D mice. NMN also enhances hepatic insulin sensitivity and restores gene expression related to oxidative stress, inflammatory response, and circadian rhythm, partly through SIRT1 activation. Furthermore, NAD+ and NAMPT levels show significant decreases in multiple organs during aging, and NMN improves glucose intolerance and lipid profiles in age-induced T2D mice. These findings provide critical insights into a novel intervention against diet- and age-induced T2D. 4 regular chow fed mice (RC1-4) vs 4 high-fat diet fed (HFD) (HFD1a-4a) mice were analyzed on one chip (Chip-A). 4 HFD mice (HFD1b-4b) vs 4 HFD-NMN treated mice (NMN1-4) were examined on the other chip (Chip-B).
2011-12-05 | E-GEOD-31647 | biostudies-arrayexpress
Project description:Through integration of whole genome CRISPR screening and pan-cancer genetic dependency mapping, we identified nicotinamide phosphoribosyltransferase (NAMPT) and nicotinamide nucleotide adenylyltransferase 1 (NMNAT1) as acute myeloid leukemia (AML) dependencies governing NAD+ biosynthesis. While both NAMPT and NMNAT1 were required for AML, we found that the presence of NAD+ precursors bypassed the dependence of AML on NAMPT, but not NMNAT1, pointing to NMNAT1 as a gatekeeper of NAD+ biosynthesis. We provide evidence that reduced nuclear NAD+ upon deletion of NMNAT1 activated p53, which is due to attenuated deacetylation by SIRT6/7 in AML cells. Our findings reveal that NAD+ is a critical metabolic foundation for AML, and NMNAT1 is a novel therapeutic target for this disease.
2021-07-28 | GSE171565 | GEO
Project description:Acetaminophen overdose is the most common cause of acute liver injury (ALI) or acute liver failure in the USA. Its pathogenetic mechanisms are incompletely understood. Additional studies are warranted to identify new genetic risk factors for more mechanistic insights and new therapeutic target discoveries. The objective of this study was to explore the role and mechanisms of nicotinamide phosphoribosyltransferase (NAMPT) in acetaminophen-induced ALI. C57BL/6 Nampt gene wild type (Nampt+/+)-, heterozygous knockout (Nampt+/-)-, and overexpression (NamptOE)-mice were treated with overdose of acetaminophen, followed by histological, biochemical, and transcriptomic evaluation of liver injury. The mechanism of Nampt in acetaminophen -induced hepatocytic toxicity was also explored in cultured primary hepatocytes. Three lines of evidence have convergently demonstrated that acetaminophen overdose triggers the most severe oxidative stress and necrosis, and the highest expression of key necrosis driving genes in Nampt+/- mice, while the effects in NamptOE mice were least severe relative to Nampt+/+ mice. These findings support that NAMPT protects against acetaminophen induced ALI.
2018-04-03 | GSE110787 | GEO
Project description:Age-related microvascular dysfunction disrupts nutrient homeostasis and waste clearance, leading to organ failure. However, a critical gap remains in our understanding of the specific molecular drivers of vascular deterioration and how they orchestrate organism-wide aging. Here, we identify progressive activation of the CCAAT/enhancer-binding protein β (C/EBPβ)/asparagine endopeptidase (AEP) pathway in aging vascular endothelial cells contributes to vascular degeneration and lifespan reduction. Endothelial-specific C/EBPβ or AEP overexpression accelerated vascular aging and shortened lifespan in mice. Mechanistically, AEP mediates proteolytic cleavage of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in nicotinamide adenine dinucleotide (oxidised form, NAD+) biosynthesis, resulting in systemic NAD⁺ depletion and senescence that elicits both central and peripheral vascular dysfunction and ultimately systemic aging. Genetic ablation of AEP or expression of AEP-resistant NAMPT N136A mutant significantly ameliorated vascular aging and extended lifespan in endothelial-specific Tie 2-C/EBPβ transgenic mice. Pharmacologically, AEP inhibitor CP#11A or nicotinamide mononucleotide (NMN) supplementation alleviated age-related vascular decline, with CP#11A showing superior efficacy. These findings support a model in which endothelial senescence contributes to vascular dysfunction and systemic aging mediated by C/EBPβ/AEP signaling, and establish C/EBPβ/AEP as a therapeutic target to preserve vascular integrity and mitigate systemic frailty in aging populations.
2026-05-30 | E-MTAB-17006 | biostudies-arrayexpress