Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Folate depletion induces erythroid differentiation through perturbation of de novo purine synthesis

ABSTRACT: Folate depletion induces erythroid differentiation through perturbation of de novo purine synthesis

PROVIDER: PRJNA1026611 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR26341875_1.fastq.gz	Fastqsanger.gz
	SRR26341875_2.fastq.gz	Fastqsanger.gz
	SRR26341876_1.fastq.gz	Fastqsanger.gz
	SRR26341876_2.fastq.gz	Fastqsanger.gz
	SRR26341877_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 48

Similar Datasets

Folate depletion induces erythroid differentiation through perturbation of de novo purine synthesis

Project description:Folate, an essential vitamin, is a one-carbon acceptor and donor in key metabolic reactions. Erythroid cells harbor a unique sensitivity to folate deprivation, as revealed by the primary pathological manifestation of nutritional folate deprivation: megaloblastic anemia. To study this metabolic sensitivity, we applied mild folate depletion to human and mouse erythroid cell lines, and primary murine erythroid progenitors. We show that folate depletion induces early blockade of purine synthesis and accumulation of the purine synthesis intermediate and signaling molecule, AICAR, followed by enhanced heme metabolism, hemoglobin synthesis, and erythroid differentiation. This is phenocopied by inhibition of folate metabolism using the SHMT1/2 inhibitor - SHIN1, and by AICAR supplementation. Mechanistically, the metabolically-driven differentiation is independent of nucleotide sensing through mTORC1 and AMPK, and is instead mediated by protein kinase C (PKC). Our findings suggest that folate deprivation-induced premature differentiation of erythroid progenitor cells is a molecular etiology to folate-deficiency induced anemia.

2024-02-07 | GSE245011 | GEO

Folate depletion induces erythroid differentiation through perturbation of de novo purine synthesis.

Project description: Not available

| S-EPMC10830111 | biostudies-literature

RNAseq in BRD4 reporter KBM7 cells (REDS1 and REDS15) with purine metabolism perturbation

Project description:To investigate the transcriptional profile in two BRD4 reporter clones (REDS1 and REDS15) with purine metabolism perturbation

2021-04-17 | GSE168099 | GEO

De Novo Purine Synthesis Mediates Circadian Control of Cell Cycle in Zebrafish (array)

Project description:Cell cycle and metabolism are two major outputs controlled by circadian rhythm in many organisms. Here we show that the three processes were linked through inosine 5'-phosphate dehydrogenase (impdh), a rate-limiting enzyme in de novo purine synthesis. We using adult zebrafish as a model system,we applied a genome-wide transcriptome approach that allowed us to investigate circadian gene expression. The whole-genome transcriptome profiles of adult brain in time-series were assayed on Agilent zebrafish microarrays. We used a similar statistical method to identify zebrafish circadian genes (ZCOG) as our previous study in larval zebrafish. Three isoforms of impdh show strong circadian oscillations in different tissues of zebrafish. impdh1a contributes to the ocular development and pigment synthesis, impdh2 promotes and impdh1b delays the development. By limiting the GTP required by DNA synthesis, impdh2 contributes to the daily rhythm of S phase in cell cycle. Multiple enzymes in the de novo purine synthesis pathway show the same circadian oscillations with peaks similar to impdh2. The circadian expression of this pathway is conserved in mouse liver. In summary, we show that the circadian regulation of de novo purine synthesis that supplies crucial building blocks for DNA replication is critical for gating cell cycle in circadian rhythm. Adult zebrafish were sacrificed and dissected at 4h intervals starting at CT0 in both LD and DD conditions for 12 time points. Total RNA of individual zebrafish brain was extracted using Trizol (Invitrogen, Carlsbad, CA) according to the manufacturerM-bM-^@M-^Ys instruction. Microarrays were manufactured by Agilent Technologies (Agilent Technologies, Palo Alto, CA), containing 43,603 probes for zebrafish whole-genome transcriptional profiling.

2013-10-01 | E-GEOD-51277 | biostudies-arrayexpress

Dysregulated purine metabolism in DIPG reveals new treatment strategies with old drugs [ChIP-seq]

Project description:Diffuse intrinsic pontine glioma (DIPG) is a devastating brainstem cancer in children, with a median survival of under one year and limited treatment options. Over 80% of DIPGs possess a H3K27M mutation. To identify metabolic vulnerabilities linked to this mutation, we utilized a multi-omics approach in H3K27M-expressing cells, patient-derived cell lines, and mouse models. We show that by reprogramming chromatin landscape the mutation aberrantly induces NFI transcriptional activity, leading to misregulated purine and folate metabolism. Specifically, the mutation amplifies purine biosynthesis and degradation via the enzymes ATIC and PNP, respectively. Unregulated purine degradation makes DIPGs reliant on purine biosynthesis and targeting ATIC reduced tumor progression and improved survival in mice. Upregulation of the reduced folate carrier SLC191A elevated folate levels in DIPG causing antifolate resistance. However, folate removal from the microenvironment sensitized DIPGs to antifolates. We propose ATIC as a potential target and advocate for revisiting antifolate-based treatments in DIPG.

2026-09-14 | GSE249165 | GEO

Dysregulated purine metabolism in DIPG reveals new treatment strategies with old drugs [ATAC-seq]

2026-09-14 | GSE249164 | GEO

Dysregulated purine metabolism in DIPG reveals new treatment strategies with old drugs [RNA-seq]

2026-09-14 | GSE249166 | GEO

De Novo Purine Synthesis Mediates Circadian Control of Cell Cycle in Zebrafish (array)

2013-10-01 | GSE51277 | GEO

BRD4-chromatin interaction in reporter KBM7 cells (REDS15) with purine metabolism perturbation

Project description:BRD4-chromatin interaction in reporter KBM7 cells (REDS15) with purine metabolism perturbation

| PRJNA704409 | ENA

RNAseq in BRD4 reporter KBM7 cells (REDS1 and REDS15) with purine metabolism perturbation

Project description:RNAseq in BRD4 reporter KBM7 cells (REDS1 and REDS15) with purine metabolism perturbation