Unknown,Transcriptomics,Genomics,Proteomics

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IMPC (international mouse phenotyping consortium) high throughput RNA seq of 1143 samples from 106 IMPC knockout lines

ABSTRACT: A RNA Seq analysis of 7 tissues from 16 week old male knockout mice. A total of 106 IMPC knockout lines were analysed by David West's group at Children's Hospital Oakland Research Institute.

INSTRUMENT(S): Illumina HiSeq 2500, Illumina HiSeq 4000

ORGANISM(S): Mus musculus

SUBMITTER: Mouse Informatics

PROVIDER: E-MTAB-5131 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Background: In a recent intervention study, the daily supplementation with 200 mg monomeric and oligomeric flavanols (MOF) from grape seeds for 8 weeks revealed a vascular health benefit in male smokers. The objective of the present study was to determine the impact of MOF consumption on the gene expression profile of leukocytes and to assess changes in DNA methylation. Methodology/Principal Findings: Gene expression profiles were determined using whole genome microarrays (Agilent) and DNA methylation was assessed using HumanMethylation450 BeadChips (Illumina). MOF significantly modulated the expression of 864 genes. The majority of the affected genes are involved in chemotaxis, cell adhesion, cell infiltration or cytoskeleton organisation, suggesting lower immune cell adhesion to endothelial cells. This was corroborated by in vitro experiments showing that MOF exposure of monocytes attenuates their adhesion to TNF-M-NM-1-stimulated endothelial cells. Nuclear factor-kappa B (NF-M-NM-:B) reporter gene assays confirmed that MOF decrease the activity of NF-M-NM-:B. Strong inter-individual variability in the leukocytesM-bM-^@M-^Y DNA methylation was observed. As a consequence, on group level, changes due to MOF supplementation could not be found. However, in individuals, significant changes in DNA methylation of genes involved in leukocyte rolling, adhesion and cytoskeleton remodelling were seen. Conclusion: Our study revealed that regular consumption of MOF modulates the expression of genes in immune cells which, however, cannot be correlated to alterations in the DNA methylome. Remarkably, at the individual level, genes related to leukocyte adhesion pathways present complex variation in DNA methylation. As such, the individual transcriptional and epigenetic modulation of genes involved in early manifestation of cardiovascular diseases constitutes important subcellular mechanisms by which MOF promote vascular health in humans. DNA methylation levels of blood samples from 10 subjects were assessed using HumanMethylation450 BeadChips (Illumina), both before and after a diet intervention with MOF.

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IMPC (international mouse phenotyping consortium) high throughput RNA seq of 1143 samples from 106 IMPC knockout lines

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