Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Expression data from tumoral thymocytes and DP thymocytes expressing an activated form of b-catenin in mouse T cells

ABSTRACT: To assess the importance of the Wnt pathway during T cell develoment, we generated a mouse line (R26-M-NM-2cat) in which high levels of active M-NM-2-catenin are maintained throughout T cell development. Young R26-M-NM-2cat mice (6-week-old) show a differentiation block at the CD4+CD8+ DP stage. All R26-M-NM-2cat mice develop T cell leukemias with a DP phenotype at 5-6 months of age. To identify the molecular pathways involved in tumor development, we profiled the global gene expression of transformed and pre-transformed DP cells. Thymocytes from 6-week-old mice (with a normal sized thymus and a polyclonal thymocyte population) were used to define the pre-transformed transcriptome. RNA from control and pre-leukemic R26-M-NM-2cat DP thymocytes as well as R26-M-NM-2cat total tumor cells were extracted and used for transcriptome analysis.

ORGANISM(S): Mus musculus

SUBMITTER: Peggy Kirstetter

PROVIDER: E-GEOD-48203 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

β-Catenin activation synergizes with Pten loss and Myc overexpression in Notch-independent T-ALL.

Kaveri Deepika D Kastner Philippe P Dembélé Doulaye D Nerlov Claus C Chan Susan S Kirstetter Peggy P

Blood 20130625 5

Wnt signaling is important for T-cell differentiation at the early CD4(-)CD8(-) stage and is subsequently downregulated with maturation. To assess the importance of this downregulation, we generated a mouse line (R26-βcat) in which high levels of active β-catenin are maintained throughout T-cell development. Young R26-βcat mice show a differentiation block at the CD4(+)CD8(+) double-positive (DP) stage. These DP cells exhibit impaired apoptosis upon irradiation or dexamethasone treatment. All R2 ...[more]

PMID: 23801632

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Project description:Glucocorticoids play a role in regulation of T lymphocytes homeostasis and development. In particular, glucocorticoid treatment induces massive apoptosis of CD4+CD8+ double positive (DP) thymocytes. This effect is due to many mechanisms, mainly driven by modulation of gene transcription. To find out which genes are modulated, we analyzed DP thymocytes treated for 3 hours with dexamethasone or medium alone, by global gene expression profiling using the Affymetrix technology (MGU74Av2 GeneChip). The data were analyzed with MAS 5.0 imposing a cut off of 1.7 fold in up regulation and 1.35 fold in down regulation. To further filter results we also used the statistical software, SAM (d 0.88 see figure 1s in supplementary data of the above cited manuscript). Results indicate modulation of 156 genes, also confirmed by either RNAse protection assay or Real Time PCR. For data mining we also used Go Miner to explore the Gene Ontology data bank (see tables 1-3 of the above cited manuscript). The overall results demonstrated that dexamethasone caused the down-regulation of genes promoting survival of DP thymocytes (e.g. Notch1, Socs1 and Id3) or the modulation of genes activating cell death through the ceramide pathway (Ugcg, Sgpp1, Degs1 and Gpr65) or through the mithocondrial machinery. Among the latter, there are Bcl-2 family members (Bim, Bfl-1, Bcl-xL and Bcl-xbeta), genes involved in the control of redox status (thioredoxin reductase, TXNIP and idh2) and genes belonging to Tis11 family which are involved in mRNA stability. Our study suggests that dexamethasone treatment of DP thymocytes modulates several genes belonging to apoptosis-related systems that can contribute to their apoptosis. Experiment Overall Design: Thymi from 4 week old C3H/HeN mice were teased in culture medium, CD4+CD8+ double positive (DP) thymocytes were sorted with microbeads Miltenyi Biotech methods and were plated in 6 well plates with 3 ml of the culture medium at a concentration of 5.0E+06 cell/ml together with 1E-07 M Dexamethasone or a corresponding volume of PBS. DP thymocytes were kept at 37Â°C, 5% CO2 in a humidified atmosphere for 3 hours. Total RNA was extracted and analyzed. We used 2 technical replicate-extracts.

Dataset Information

Expression data from tumoral thymocytes and DP thymocytes expressing an activated form of b-catenin in mouse T cells

Publications

β-Catenin activation synergizes with Pten loss and Myc overexpression in Notch-independent T-ALL.

Similar Datasets

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