Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Infiltration of monocyte-derived macrophages perturbs the CNS metabolic landscape, licensing arginine catabolism and augments neuro-inflammation

ABSTRACT: Infiltration of monocyte-derived macrophages perturbs the CNS metabolic landscape, licensing arginine catabolism and augments neuro-inflammation

PROVIDER: PRJNA966117 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Infiltration of monocyte-derived cells perturbs CNS metabolism, licensing arginine catabolism augmenting neuroinflammation

Project description:Inflammatory responses are associated with recruitment of monocyte-derived cells (Mdcs) into tissues. While tissue-specific Mdc reprogramming is well-established, how Mdc inflitration alters tissue metabolism remains unclear. Here, using a murine neuroinflammation model coupled with genetic fate-mapping, metabolomics, and metabolite imaging, we identify that central nervous system (CNS) Mdc infiltration is associated with substantial metabolic changes, assigning disease-linked metabolites (DLMs) therein. Particularly, we found increased arginine catabolism driven by lesion-associated Arginase-1 (Arg1)-expressing Mdcs promoted oxidative damage, lipid accumulation and Mdc dysfunction. Genetic Arg1-deficiency within Mdcs during neuroinflammation increased extracellular arginine and was associated with rewiring of the CNS metabolic landscape, including attenuated DLMs. This was accompanied by enhanced Mdc-driven anti-inflammation, regulatory T cell expansion, and improved disease outcome. Opposing effects were observed upon dietary arginine deficiency. Together, our work highlights key roles for Mdcs in CNS metabolism and reveals the pleiotropic beneficial effects of arginine in neuroinflammation.

2026-04-07 | GSE231474 | GEO

How interdiction of inositol pyrophosphate catabolism perturbs the fission yeast response to phosphate starvation

Project description:How interdiction of inositol pyrophosphate catabolism perturbs the fission yeast response to phosphate starvation

| PRJNA1419851 | ENA

H2A.Z Facilitates Licensing and Activation of Early Replication Origins

Project description:DNA replication is a tightly regulated process that ensures the precise duplication of the genome during cell cycle. Licensing and activation of eukaryotic replication origins are controlled primarily by chromatin. However, the chromatin features involved and the regulatory mechanism remain largely unknown. In this study, we found that H2A.Z binds Suv420H1 directly to promote H4K20me2 deposition on nucleosome both in vitro and in vivo. ORC1 is subsequently recruited to chromatin for licensing and activation of early replication origins. Depletion of H2A.Z results in defects of DNA replication and cell proliferation in both HeLa cells and T cells. Thus, our results provide novel mechanistic insights that the histone variant H2A.Z epigenetically regulates licensing and activation of the early DNA replication origins through the Suv420H1-H4K20me2-ORC1 pathway.

2019-09-22 | GSE134988 | GEO

Chronic p53-independent p21 expression deregulates replication licensing, leading to genomic instability

Project description:P53 independent P21 expression deregulates replication licensing , leading to genomic instability

2016-05-17 | PXD004140 | Pride

Temporal control of human DNA replication licensing by CDK4/6-RB signalling and chemical genetics

Project description:Cyclin-dependent kinases (CDKs) coordinate DNA replication and cell division, and play key roles in tissue homeostasis, genome stability and cancer development. The first step in replication is origin licensing, when minichromosome maintenance (MCM) helicases are loaded onto DNA by CDC6, CDT1 and the origin recognition complex (ORC). In yeast, origin licensing starts when CDK activity plummets in G1 phase, reinforcing the view that CDKs inhibit licensing. Here we show that, in human cells, CDK4/6 activity promotes origin licensing. By combining rapid protein degradation and time-resolved EdU-sequencing, we find that CDK4/6 activity acts epistatically to CDC6 and CDT1 in G1 phase and counteracts RB pocket proteins to promote origin licensing. Therapeutic CDK4/6 inhibitors block MCM and ORC6 loading, which we exploit to trigger mitosis with unreplicated DNA in p53-deficient cells. The CDK4/6-RB axis thus links replication licensing to proliferation, which has implications for human cell fate control and cancer therapy design.

2025-08-14 | GSE278714 | GEO

Augmenting CAR T Cell Function with LIGHT

Project description:Augmenting CAR T Cell Function with LIGHT

| PRJNA1005966 | ENA

Arginine catabolism and polyamine biosynthesis pathway disparities within Francisella tularensis subpopulations

Project description:Arginine catabolism and polyamine biosynthesis pathway disparities within Francisella tularensis subpopulations

| PRJNA837875 | ENA

Arginine catabolism and polyamine biosynthesis pathway disparities within Francisella tularensis subpopulations

Project description:Francisella tularensis is a highly infectious zoonotic pathogen with as few as 10 organisms causing tularemia, a disease that is fatal if untreated. Although F. tularensis subspecies tularensis (type A) and subspecies holarctica (type B) share over 99.5% average nucleotide identity, notable differences exist in genomic organization and pathogenicity. The type A clade has been further divided into subtypes A.I and A.II, with A.I strains being recognized as some of the most virulent bacterial pathogens known. In this study, we report on major disparities that exist between the F. tularensis subpopulations in arginine catabolism and subsequent polyamine biosynthesis. The genes involved in these pathways include the speDEA and aguAB operons, along with metK. In the hypervirulent F. tularensis A.I clade, such as the A.I prototype strain SCHU S4, these genes were found to be intact and highly transcribed. In contrast, both subtype A.II and type B strains have a truncated speA gene, while the type B clade also has a disrupted aguA and truncated aguB. Ablation of the chromosomal speE gene that encodes a spermidine synthase reduced subtype A.I SCHU S4 growth rate, whereas the growth rate of type B LVS was enhanced. These results demonstrate that spermine synthase SpeE promotes faster replication in the F. tularensis A.I clade, whereas type B strains do not rely on this enzyme for fitness. Our ongoing studies on metabolism should provide a better understanding of the factors that contribute to F. tularensis pathogenicity.

2022-07-13 | GSE202948 | GEO

cAMP Signaling Regulates DNA Demethylation by Augmenting the Intracellular Labile Ferrous Iron Pool

Project description:In this study we show that cAMP helps regulate cytosine demethylation through augmenting the intracellular labile ferrous iron pool.

2018-01-01 | GSE101153 | GEO