Whole Genome Expression Array in Human T-cell Acute Lymphoblastic Leukemia
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: ozden hatirnazng
PROVIDER: E-GEOD-46170 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Single cell suspensions of total thymocytes were obtained from Pten enhancer (PE) wild-type or knockout mice. This single-cell suspension was enriched in CD4-CD3- immature thymocyte progenitor cells. CD4-CD3- enriched thymocytes were then mixed 1:1 with single-cell suspensions from total unenriched thymocytes and subsequntly loaded in a 10x Chromium instrument for single-cell RNAseq analyses. Our results revealed Pten levels are signifcantly decreased in CD4-CD8- double negative (DN) thymocytes, CD8+ intermediate single positive (ISP) thymocytes and CD4+CD8+ double positive (DP) thymocytes in PE knockout mice, compared to PE wild-type mice.
2020-12-17 | GSE156070 | GEO
Project description:Subpopulations of human fetal thymocyte and circulating naïve T cells were obtained through FACS sorting, including CD3-CD4+CD8- intrathymic T progenitor cells (ITTP), CD3intCD4+CD8+ "double positive" thymocytes (DP), CD3highCD4+CD8- "single positive" thymocytes (SP4), CD3+CD4+CD8-CD45RA+CD62L+ naïve T cells from cord blood (CB4+), and CD3+CD4+CD8-CD45RA+CD62L+ naïve T cells from adult blood (AB4+).
2007-08-06 | E-GEOD-1460 | biostudies-arrayexpress
Project description:Subpopulations of human fetal thymocyte and circulating naïve T cells were obtained through FACS sorting, including CD3-CD4+CD8- intrathymic T progenitor cells (ITTP), CD3intCD4+CD8+ "double positive" thymocytes (DP), CD3highCD4+CD8- "single positive" thymocytes (SP4), CD3+CD4+CD8-CD45RA+CD62L+ naïve T cells from cord blood (CB4+), and CD3+CD4+CD8-CD45RA+CD62L+ naïve T cells from adult blood (AB4+). Keywords = Microarray Keywords = gene expression Keywords = thymocytes Keywords = naïve CD4+ T cell Keywords = recent thymic emigrants Keywords: other
2004-07-01 | GSE1460 | GEO
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:The (pro)renin receptor (PRR) was originally thought to be important in regulating blood pressure via the renin-angiotensin system (RAS), however it is emerging that PRR is instead generally essential for cellular development via its involvement in Wnt signalling. Here, we have specifically deleted PRR from T cells, which require Wnt for their development. T cell-specific PRR-knockout (cKO) mice (ATP6AP2flox/y;Lck-CRE) had a significant decrease in thymic cellularity, corresponding with a 100-fold decrease in the number of CD4+ and CD8+ thymocytes, and a large increase in double negative (DN) precursors. Further characterisation of DN T cell progenitors revealed that deletion of PRR impaired T cell development at multiple stages; including transition from DN3(CD25+CD44-) - DN4(CD25-CD44-), DN4-CD4+ CD8+ double positive (DP), DP-intermediate single positive (CD3-CD8+ ISP) cells. We performed gene expression analysis on sorted DN3 T cells, which indicated that PRR cKO T cells have perturbations in key cellular pathways essential at the DN3 stage, such as RNA processing and translation. Our study identifies a new role for PRR in multiple facets of T cell development, and gives further support to the notion that PRR is generally essential for cellular development.
2015-07-01 | E-MTAB-3568 | biostudies-arrayexpress
Project description:LMO2 overexpressing transgenic mouse models suggest an accumulation of immature T-cell progenitors in the thymus as main pre-leukemic event. The effects of LMO2 overexpression on human T-cell development in vivo, however, are unknown. Here we report studies of a humanized mouse model transplanted with LMO2 transduced human hematopoietic stem and progenitor cells. The effects of LMO2 overexpression were confined to the T-cell lineage although initially multipotent cells were transduced. Three effects of LMO2 on human T-cell development were observed: 1) a block at the DN/ISP stage, 2) an accumulation of CD4+CD8+ double positive CD3- cells and 3) an altered CD8/CD4 ratio with enhanced peripheral T lymphocytes Single stranded cDNA was synthesized from 1000 pg total RNA using the Ovation Pico WTA System V2 Module (NuGEN Technologies Inc, Leek, The Netherlands) in combination with the Encore Biotin Module (NuGEN Technologies Inc) according to the instructions of the manufacturer. Biotin labeling and fragmentation was performed and fragmented cDNA was hybridized onto Affymetrix Gene Atlas human U219 arrays.
2016-03-26 | E-GEOD-79625 | 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:Calicum plays critical roles in developing T cells, promoting survival, proliferation, and differentiation at multiple stages of maturation. Calcium release from intracellular stores due to T cell receptor and pre-T cell receptor signaling is thought to require the inositol triphosphate receptors (Itpr), however the requirement for these receptors has not been investigated. We used microarrays to examine gene expression differences between control and Itpr deficient T cell progenitors. We used microarrays to identify changes in the transcriptional programme of developing T cells prior to acquisition of a mature T cell receptor and identified several developmentally important genes altered in the absence of Itpr. Thymocyte progenitors at DN4 or ISP were harvested for RNA extraction from three independent control Itpr1/Itpr2/Itpr3 triple homozygous floxed (CTL) or Tie2-Cre Itpr1/Itpr2/Itrp3 triple homozygous floxed (KO) thymii, pooled, and hybridized on Affymetrix microarrarys. To obtain a homogenous population of thymocyte progenitors, we FACS purified cells and collect RNA from only DN4 or ISP T cells. ISP T cells were defined as CD4- CD8+ CD24+ CD3-. DN4 T cells were defined as CD45+ CD24+ CD3- CD4- CD8- CD25- CD44- CD19- B220- gdTCR- Ter119- Mac1- Gr1-. Thymocytes were harvested from neonatal mice, ranging from 7 to 10 days of age and lacked any signs of malignancy or disease.
2014-05-28 | E-GEOD-57997 | biostudies-arrayexpress
Project description:LMO2 overexpressing transgenic mouse models suggest an accumulation of immature T-cell progenitors in the thymus as main pre-leukemic event. The effects of LMO2 overexpression on human T-cell development in vivo, however, are unknown. Here we report studies of a humanized mouse model transplanted with LMO2 transduced human hematopoietic stem and progenitor cells. The effects of LMO2 overexpression were confined to the T-cell lineage although initially multipotent cells were transduced. Three effects of LMO2 on human T-cell development were observed: 1) a block at the DN/ISP stage, 2) an accumulation of CD4+CD8+ double positive CD3- cells and 3) an altered CD8/CD4 ratio with enhanced peripheral T lymphocytes
2016-03-26 | GSE79625 | GEO
Project description:CD8+ and CD4+ T cells from HIV infected patients with HIV-RNA viremia of >50 copies/ml and CD8+ and CD4+ T cells from healthy controls were isolated by negative selection (Miltenyi Biotech, Auburn, CA). Cell sorting of the CD4 and CD8 T cell subsets were performed based on surface staining of CD3+CD8+ or CD3+CD4+ and na ve CD45RA+CD27+CD127highHLA-DRlow, and CD3+CD8+ or CD3+CD4+ and memory CD45RA-CD27+CD127highHLA-DRlow. Sorted cell populations were spun down and stored as dry pellets at -80M-BM-0C. Samples analyzed by transcript levels of genes related to cytokine signaling were determined by the JAK/STAT Signaling Pathway microarray. CD8+ and CD4+ T cells from HIV infected patients with HIV-RNA viremia of >50 copies/ml and CD8+ and CD4+ T cells from healthy controls were isolated by negative selection (Miltenyi Biotech, Auburn, CA). Cell sorting of the CD4 and CD8 T cell subsets were performed based on surface staining of CD3+CD8+ or CD3+CD4+ and naM-CM-/ve CD45RA+CD27+CD127highHLA-DRlow, and CD3+CD8+ or CD3+CD4+ and memory CD45RA-CD27+CD127highHLA-DRlow. Sorted cell populations were spun down and stored as dry pellets at -80M-BM-0C. Samples analyzed by transcript levels of genes related to cytokine signaling were determined by the JAK/STAT Signaling Pathway microarray (http://www.sabiosciences.com/rt_pcr_product/HTML/PAHS-039A.html, SABiosciences Frederick, MD). Briefly, total RNA was harvested from each individual T cell subset from each patient or healthy control and contaminating DNA was digested with DNase. Messenger RNA was converted to cDNA and loaded onto PCR array plates for quantitative real-time PCR. Quantification of transcript levels was determined by normalizing to 5 housekeeping genes from each individual sample. Relative gene expression levels for each subset were averaged and compared between cell populations from the patient group and healthy controls. Because of the multiple comparisons only p values M-bM-^IM-$ 0.01 were considered significant.
2010-12-28 | E-GEOD-25456 | biostudies-arrayexpress