Memory T cells are important for protective immunity against infectious microorganisms. Such protection is achieved by cooperative action of memory T cell populations that differ in their tissue localization and functionality. We report on the identification of the fractalkine receptor CX3CR1 as marker for stratification of memory T cells with cytotoxic effector function from those with proliferative function in both, mice and man. Based on CX3CR1 and CD62L expression levels four distinct memory T cell populations can be distinguished based on their functional properties. Transcriptome and proteome profiling revealed that CX3CR1 expression was superior to CD62L to resolve memory T cell functionality and allowed determination of a core signature of memory T cells with cytotoxic effector function. This identifies a CD62Lhi CX3CR1+ memory T cell population with an identical gene signature to CD62LlowCX3CR1+ effector memory T cells. In lymph nodes, this so far unrecognized CD62LhiCX3CR1+ T cell population shows a distinct migration pattern and anatomic positioning compared to CD62LhiCX3CR1neg TCM. Furthermore, CX3CR1+ memory T cells were scarce or absent during chronic HBV, HCV and HIV infection in man and chronic LCMV infection in mice confirming the value of CX3CR1+ in understanding principles of protective immune memory. Overall design: CD8+ T cells were isolated and directly assessed. After harvesting, cells were immediately lysed in Trizol (Invitrogen) before storage at -80°C for RNA isolation.
Functional classification of memory CD8(+) T cells by CX3CR1 expression.
No sample metadata fields
View SamplesIn this survey we effectively combined transcriptomics, proteomics and targeted-metabolomics to analyse the temporal relationship of alterations in liver preceding and accompanying the development of HFD-mediated hepatic insulin resistance. To assess HFD-mediated alterations in physiological parameters, insulin sensitivity, and molecular adaptations in liver male C3HeB/FeJ mice treated with a high-fat diet (HFD) for 7, 14, or 21 days and compared to age- matched controls fed low-fat diet (LFD).
High fat diet-induced modifications in membrane lipid and mitochondrial-membrane protein signatures precede the development of hepatic insulin resistance in mice.
Sex, Age, Treatment, Time
View SamplesThe purpose of current study is to identify the differentiated gene expression associated with mouse 11B3 deletion, syntenic to human chromosome 17p13.1. We compared four different mouse acute myeloid leukemia cells, freshly isolated from mouse bone marrows with either 11B3fl/p53fl;shNf1;shMll3;Vav1-Cre or p53fl/fl;shNf1;shMll3;Vav1-Cre. The RNA-seq results indicate that genes located on chromosome 11B3 mostly reduce gene expression level in 11B3 deleted leukemia cells. Overall design: Examination RNA expression level in 11B3-deleted vs p53-loss only samples.
Deletions linked to TP53 loss drive cancer through p53-independent mechanisms.
No sample metadata fields
View SamplesWe compared gene expression profiles between asymptomatic and symptomatic atherosclerotic plaques from the same patient. This was accomplished by analyzing carotid plaques from four patients with bilateral high-grade carotid artery stenoses one being symptomatic (TIA or stroke) and the other asymptomatic.
Microarray analysis reveals overexpression of CD163 and HO-1 in symptomatic carotid plaques.
Sex, Age, Specimen part, Disease, Disease stage, Subject, Time
View SamplesThe aim of the experiment was to compare to single and combined effect of Ikaros activation and IL-7 withdrawal in the Ikaros-null pre-B cell line BH1
Ikaros is absolutely required for pre-B cell differentiation by attenuating IL-7 signals.
Specimen part
View SamplesEstablishing reliable biomarkers for assessing and validating clinical diagnosis at early prodromal stages of Parkinsons disease is crucial for developing therapies to slow or halt disease progression. Here, we present the largest study to date using whole blood gene expression profiling from over 500 individuals to identify an 87-gene blood-based signature. Our gene signature effectively differentiates between idiopathic PD patients and controls in both a validation cohort and an independent test cohort, and further highlights mitochondrial metabolism and ubiquitination/proteasomal degradation as potential pathways disrupted in Parkinsons disease.
Analysis of blood-based gene expression in idiopathic Parkinson disease.
Sex, Specimen part, Subject
View SamplesFluorine-18-fluoro-2-deoxy-D-glucose (FDG) is widely used as positron-emission-tomography (PET) radiotracer for the detection and staging of human cancer. Tumor uptake of FDG varies substantially between different cancer types and between patients with the same tumor type. The molecular basis for this heterogeneity is unknown. Using cancer cell lines and primary human tumors of distinct histologic origins, we here show that increased FDG uptake is universally associated with coordinate upregulation of genes within the glycolysis, pentose-phosphate, and other related metabolic pathways. In primary human breast cancers, this FDG signature shows significant overlap with established breast cancer signatures for the basal-like disease subtype and poor prognosis. FDG high breast cancer showed significantly more gene copy number alterations genome wide than FDG low cancers. About 50 % of primary breast cancers with high FDG uptake and FDG gene expression signature show DNA copy gain encompassing the c-myc gene locus and express gene sets regulated by the transcription factor MYC. Our data shows that FDG-PET marks a distinct subset of basal-like human breast cancer which is characterized by MYC and prognostically unfavorable gene expression signatures, suggesting that FDG-PET imaging may be useful to risk-stratify patients with locally advanced breast cancer.
18F-fluorodeoxy-glucose positron emission tomography marks MYC-overexpressing human basal-like breast cancers.
Specimen part, Cell line
View SamplesWe have observed that follicular B cells from mice with a hypomorphic mutation (IkL/L) in the Ikzf1 gene (which encodes the Ikaros transcription factor) exhibit an increased proliferative response to anti-IgM stimulation (Kirstetter et al, Eur J Immunol, 32:720-30, 2002). We asked if Ikaros controls the transcriptional response that unfolds after activation, or if differences in the transcriptional landscape of resting B cells could explain the altered response. To this end, we have determined the transcriptome of unstimulated WT and IkL/L follicular B cells, as well as that of cells stimulated for 3h and 12h with anti-IgM. Samples from 2 independent experients were analyzed.
Ikaros limits follicular B cell activation by regulating B cell receptor signaling pathways.
Age, Specimen part
View SamplesIn order to explore the funciton of p53 splice variant in DNA damage response, we utilized CRISPR-cas9 genome editing technique to specifically knock out this variant in MCF7 cells.
Identification of a DNA Damage-Induced Alternative Splicing Pathway That Regulates p53 and Cellular Senescence Markers.
Treatment
View SamplesIkaros hypomorphic mice (IkL/L) show plasmacytoid dendritic cell (pDC) defects with an absence of pDCs in the peripheral organs and a reduction of pDCs in the bone marrow (BM). Moreover in vitro differentiation of pDC from IkL/L total BM cells is also defective.
Ikaros cooperates with Notch activation and antagonizes TGFβ signaling to promote pDC development.
Treatment
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