Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA262920 | ENA |
REPOSITORIES: ENA
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Project description:Development of gene expression signatures with lncRNAs for coculture of CD34+ T-cells with an OP9-DLL1 feeder layer
| PRJNA262919 | ENA
Project description:The transcription factor Thpok is essential for CD4 T cell development in the thymus and remains expressed in post-thymic CD4 T cells. We post-thymically inactivated Thpok and compared microarray gene expression in Thpok-deficient CD4 T cells to that in their wildtype CD4 or CD8 counterparts We show that Thpok constrains the transcriptional circuitry to maintain CD4+-lineage integrity in naM-CM-/ve cells and to couple effector differentiation to environmental cues after antigenic stimulation. Redundantly with the related factor LRF, Thpok is continuously needed to prevent the trans-differentiation of mature CD4+ into -CD8+ T cells. We activated naM-CM-/ve CD4 T cells (either wild-type or Thpok-deficient) and CD8 T cells (wild-type) in vitro under Th1 conditions. Differentiated effectors were sorted 4 days after activation into CD4+CD8- and CD4-CD8+ (wild-type) and CD4+CD8- and CD4+CD8+ (Thpok-deficient) subsets. Total RNA was extracted from sorted subsets and processed for microarray analyses (Affymetrix Mouse Exon 1.0 ST array) at the NCI microarray facility, following the manufacturerM-bM-^@M-^Ys recommendation. Data is from 3 replicates (except wild-type CD4-CD8+ cells, for which two samples only were processed), generated from two distinct cell preparations.
2014-08-15 | E-GEOD-57846 | biostudies-arrayexpress
Project description:The Tec-family kinase Itk plays an important role during T-cell activation and function, and controls also conventional versus innate-like T-cell development. We have characterized the transcriptome of Itk-deficient CD3+ T-cells, including CD4+ and CD8+ subsets, using Affymetrix microarrays. The largest difference between Itk-/- and Wt CD3+ T-cells was found in unstimulated cells, e.g. for killer cell lectin-like receptors. Compared to anti-CD3-stimulation, anti-CD3/CD28 significantly decreased the number of transcripts suggesting that the CD28 co-stimulatory pathway is mainly independent of Itk. The signatures of CD4+ and CD8+ T-cell subsets identified a greater differential expression than in total CD3+ cells. Cyclosporin (CsA)-treatment had a stronger effect on transcriptional regulation than Itk-deficiency, suggesting that only a fraction of TCR-mediated calcineurin/NFAT-activation is dependent on Itk. Bioinformatic analysis of NFAT-sites of the group of transcripts similarly regulated by Itk-deficiency and CsA-treatment, followed by chromatin-immunoprecipitation, revealed NFATc1-binding to the Bub1, IL7R, Ctla2a, Ctla2b, and Schlafen1 genes. Finally, to identify transcripts that are regulated by Tec-family kinases in general, we compared the expression profile of Itk-deficient T-cells with that of Btk-deficient B-cells and a common set of transcripts was found. Taken together, our study provides a general overview about the global transcriptional changes in the absence of Itk. Experiment Overall Design: CD3+ CD4+ and CD8+ T-cells from pooled suspensions of spleen and lymph nodes of Wt and Itk knockout mice on C57BL/6 background were isolated after negative depletion. Unstimulated as well as stimulated T-cells were studied. Stimulations were done with anti-CD3 (1 mg/ml) for 24 hrs. For the CD4+ T-cells we collected triplicates from the Itk knockout mice and duplicates from the Wt group. For the CD8+ T-cells, we got duplicates from Itk knockout , while we obtained a single sample from Wt owing to the low cell yield for resting Wt CD8+ T-cells. After CD3-stimulation we got a single sample from the CD8+ subset of both Wt and Itk knockout, while for the CD4+ subsets we collected duplicates.
2009-05-29 | E-GEOD-12465 | biostudies-arrayexpress
Project description:T cells develop from progenitors that migrate from the bone marrow into the thymus. Thymocytes are subdivided roughly as being double negative (DN), double positive (DP), or single positive (SP), based on the expression of the CD4 and CD8 coreceptors. The DN stage is heterogeneous and can be subdivided into four distinct subsets in mice based on the expression of CD44 and CD25. In human, three distinct DN stages can be recognized: a CD34+CD38−CD1a− stage that represents the most immature thymic subset and the consecutive CD34+CD38+CD1a− and CD34+CD38+CD1a+ stages. Human DN thymocytes mature via an immature single positive (ISP CD4+) and a DP stage into CD4+ or CD8+ SP T cells that express functional T cell receptors (TCR) and that exit the thymus. In this study, gene expression was measured in each of these nine stages.
2010-06-28 | GSE22601 | GEO
Project description:Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.
| S-EPMC2531291 | biostudies-literature
Project description:Development of gene expression signatures with lncRNAs for GSI treatment of T-ALL cell lines
| PRJNA262916 | ENA
Project description:Development of gene expression signatures with lncRNAs for GSI treatment of the CUTLL1 cell line.
| PRJNA262915 | ENA
Project description:Disturbed expression of microRNAs (miRNAs) in regulatory T-cells (Tregs) leads to development of autoimmunity in experimental mouse models. However, the miRNA expression signature characterizing Tregs of autoimmune diseases, such as rheumatoid arthritis (RA) has not been determined yet. Moreover, the technical limitations prevented the analysis of such minute T-cell population as naive and memory Tregs. In this study we have used a microarray approach to comprehensively analyze miRNA expression signatures of naive Tregs (CD4+CD45RO-CD25++), memory Tregs (CD4+CD45RO+CD25+++), as well as conventional naive (CD4+CD45RO-CD25-) and memory (CD4+CD45RO+CD25-) T-cells (Tconvs) derived from peripheral blood of RA patients, and matched healthy controls. Differential expression of selected miRNAs was validated by TaqMan-based qRT-PCR. We found a positive correlation between increased expression of miR-451 in T-cells of RA patients and disease activity score (DAS28), ESR levels, and serum levels of IL-6. Moreover, we found characteristic, disease and treatment independent, global miRNA expression signatures defining naive Tregs, memory Tregs, naive Tconvs and memory Tconvs. The analysis allowed us to define miRNAs characteristic for a general naive phenotype (e.g. miR-92a), a general memory phenotype (e.g. miR-21, miR-155), and most importantly miRNAs specifically expressed in both naive and memory Tregs, defining as such the Treg phenotype (i.e. miR-146a, miR-3162, miR-1202, miR-1246a, and miR-4281). MicroRNA profiling was performed in four CD4+ T-cell subsets: naive Tconventional (CD3+CD8-CD45RO-CD25-), naive Tregulatory (CD3+CD8-CD45RO-CD25+), memory Tconventional (CD3+CD8-CD45RO+CD25-), and memory Tregulatory (CD3+CD8-CD45RO+CD25+) derived from 2 healthy controls, and 6 rheumatoid arthritis patients (total n=8).
2014-01-22 | E-GEOD-50646 | biostudies-arrayexpress
Project description:Sensitive expression profiling of T-cell subsets reveals parallel post-thymic differentiation for CD4+ and CD8+ lineages
| PRJNA98961 | ENA