Cell resilience to folate deprivation boosts aberration tolerance
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ABSTRACT:
PROVIDER: PRJNA238301 | ENA |
REPOSITORIES: ENA
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Project description:We detected numerous copy number aberrations in SNP arrays from follicular lymphoma patients. Additionally, we found an outstanding homozygous state involving folic acid-related genes. To study a hypothetical association between both traits, we cultured folate-depleted cell lines. After restoring normal medium to the cultures, we performed CGH arrays to examine the induced copy number aberrations.
2019-05-23 | GSE54919 | GEO
Project description:We detected numerous copy number aberrations in SNP arrays from follicular lymphoma patients. Additionally, we found an outstanding homozygous state involving folic acid-related genes. To study a hypothetical association between both traits, we cultured folate-depleted cell lines. After restoring normal medium to the cultures, we performed CGH arrays to examine the induced copy number aberrations.
2019-05-23 | GSE54916 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2019-05-23 | GSE54920 | GEO
Project description:Cell resilience to folate deprivation boosts aberration tolerance [Illumina]
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Project description:Cell resilience to folate deprivation boosts aberration tolerance [Agilent]
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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
Project description:What is known is that methionine-dependency is a feature of some cancers. So far, it was attributed to mutations in genes involved in the methionine de novo or salvage pathways. What is new is that in this work we propose that methionine dependency stems from an altered cellular metabolism. We provide evidence that in U251 glioblastoma cell line, only cancer stem cells -isolated as tumor spheres in non adherent conditions- are methionine dependent and not monolayer cells grown in adherent conditions. Transcriptome wide-sequencing reveals that several genes involved in cytosolic folate cycle are downregulated whereas some transcripts of genes involved in mitochondrial folate cycle are upregulated. Genome wide DNA methylation does not account for these changes in gene expression. Mass spectrometry measurements confirm that tumor spheres display low cytosolic folate cycle unable to produce enough 5-methyltetrahydrofolate to remethylate homocystein to methionine. This decreased 5-methyltetrahydrofolate bioavailability is presumably due to a reprogrammed mitochondrial folate cycle which instead of synthesizing formate, intended to fuel the cytosolic folate cycle, oxidizes the formyl group to CO2 with the attendant reduction of NADP+ to NADPH and release of tetrahydrofolate. The originality of this work resides in that it replaces methionine deprivation as a useful nutritional strategy in cancer growth control since cancer stem cells are much more tumoregenic than their non stem-like counterparts. Second, it reveals that the primary default responsible of the reprogrammation of folate metabolism originates in the mitochondria. Thus, mitochondrial enzymes could be novel and more promising anticancer targets than dihydrofolate reductase (DHFR), the current target of drug therapy linked with folate metabolism.
2019-07-01 | GSE117448 | GEO
Project description:Folate is a vitamin essential for cell growth and has been used to prevent congenital abnormalities. However, little is known about how folate affects health in older adults. We examined healthspan as a function of dietary folate intake. To begin to measure such effects, we performed a small (2x2; sex-by-diet) pilot study in the long-lived inbred mouse strain C57BL/6.
2024-02-09 | GSE245438 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE9242: Dietary folate depletion and repletion in A/J and C57BL/6J mice GSE9243: Dietary folate depletion and repletion in C57BL/6J mice, ApoE knockout mice, and choline supplemented C57BL/6J mice Keywords: SuperSeries Refer to individual Series
2010-06-20 | E-GEOD-9245 | biostudies-arrayexpress
Project description:The molecular basis linking folate deficiency to certain health conditions and developmental defects is complex and not fully understood. In this study, we examined the consequences of folate deficiency on global gene expression by microarray analysis and compared transcript levels in normal human fibroblast cells (GM03349) grown in folate deficient and sufficient medium. Keywords: folate depletion, stress response, comparative genomic hybridization
2006-11-02 | GSE3548 | GEO