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Analysis for transcriptome profiling changes in 4'-O-methylpyridoxine (OMP) treated leukemic cells

ABSTRACT: To validate the transcriptome profiling changes upon pharmacologic inhibition of PDXK, a key enzyme in vitamin B6 metabolism pathway, mouse leukemic cells were treated with PDXK inhibitor OMP. mRNA was extracted and purified for RNA_seq.

ORGANISM(S): Mus musculus

PROVIDER: GSE139892 | GEO | 2020/01/13

REPOSITORIES: GEO

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Analysis for transcriptome profiling changes in 4'-O-methylpyridoxine (OMP) treated leukemic cells

Project description:Analysis for transcriptome profiling changes in 4'-O-methylpyridoxine (OMP) treated leukemic cells

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Effect of OMP on gene expression in the olfactory epithelium

Project description:OMP is expressed only in mature olfactory sensory neurons, arguing that its function is specially suited to the needs of OSNs. However none of the properties of OMP suggest any direct role in regulating gene expression in OSNs. Our data confirms that gene expression in the olfactory epithelium of mice lacking OMP is indistinguishable from mice expressing OMP. We used affymerix M430v2.0 gene chips to cover as much of genome as possible and observed no statistically significant differences in mRNA abundance between the two genotypes.These results imply that OMPs ability to regulate signal transduction with in OSNs has little effect on gene expression and that its ability to promote mitosis in neighbouring cells (under culture conditions) is insufficiently active under normal laboratory housing conditions to generate detectable differences in gene expression patterns. Keywords: genetic modification

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RNASeq data from OMP-52M51 acute treated T-ALL PDX mice

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Transcription profiling of mouse olfactory epithelium from heterozygous and homozygouse OMP-GFP animals

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Vitamin B6 metabolism determines T cell anti-tumor responses

Project description:Targeting T cell metabolism is an established method of immunomodulation. Following activation, T cells engage distinct metabolic programs leading to the uptake and processing of nutrients that determine cell proliferation and differentiation. Redirection of T cell fate by modulation of these metabolic programs has been shown to boost or suppress immune responses in vitro and in vivo. Using publicly available T cell transcriptomic and proteomic datasets we identified vitamin B6-dependent transaminases as key metabolic enzymes driving T cell activation and differentiation. Inhibition of vitamin B6 metabolism using the pyridoxal 5’-phosphate (PLP) inhibitor, aminoxyacetic acid (AOA), suppresses CD8+ T cell proliferation and effector differentiation in a dose-dependent manner. We show that pyridoxal phosphate phosphatase (PDXP), a negative regulator of intracellular vitamin B6 levels, is under the control of the hypoxia-inducible transcription factor (HIF1), a central driver of T cell metabolism. Furthermore, by adoptive transfer of CD8 T cells into a C57BL/6 mouse melanoma model, we demonstrate the requirement for vitamin B6-dependent enzyme activity in mediating effective anti-tumor responses. Our findings show that vitamin B6 metabolism is required for CD8+ T cell proliferation and effector differentiation in vitro and in vivo. Targeting vitamin B6 metabolism may therefore serve as an immunodulatory strategy to improve anti-tumor immunotherapy.

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RNASeq of OMP and TRPC2 neuronal population of zebrafish olfactory sensory neurons

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MCL cel lines upon OMP-52M51 treatment

Project description:MCL cel lines upon OMP-52M51 treatment

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Customizing functionalized cofactor mimics to study the human pyridoxal 5'-phosphate-binding proteome

Project description:Here we apply functionalized cofactor derivatives to study vitamin B6-dependent enzymes in human cells. We are able to cover for a large fraction of the pyridoxal 5'-phosphate-binding proteome (PLP-ome) and validate our results exemplarily for two PLP-DEs. One of those, named pyridoxal 5'-phosphate binding protein (PLPBP) is characterized further including studies with chemical cross-linking combined with mass spectrometry. We proceed with an in situ PLP-DE target screen applying B6-targeting compounds revealing interesting insights into selectivity. Finally, we broaden our analysis to multiple human cell lines revealing an altered PLP-DE target profile.

2019-08-27 | PXD014771 | Pride

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Project description:We sequenced the transcriptome of 34 single olfactory sensory neurons (OSNs) manually picked from OMP-GFP mice, ensuring the cells expressed high levels of GFP, a marker of mature OSNs. We pooled the olfactory mucosa from 2 male and 2 female animals, to obtain single-cell suspensions for cell picking. We only picked healthy-looking cells. From each, we constructed libraries for single-cell RNA-sequencing, to characterise the diversity of OR genes expressed.

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