Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA209194 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Activation of b-catenin has been causatively linked to the etiology of colon cancer. Conditional stabilization of this molecule in pro-T-cells promotes thymocyte development without the requirement for preTCR signaling. We show here that activated b-catenin stalls the developmental transition from the double-positive (DP) to the single-positive (SP) thymocyte stage and predisposes DP thymocytes to transformation. b-Catenin induced thymic lymphomas have a leukemic arrest at the early DP stage. Lymphomagenesis requires Rag activity, which peaks at this developmental stage, as well as additional secondary genetic events. A consistent secondary event is the transcriptional upregulation of c-Myc, whose activity is required for transformation since its conditional ablation abrogates lymphomagenesis. In contrast, the expression of Notch receptors as well as targets is reduced in DP thymocytes with stabilized b-catenin and remains low in the lymphomas indicating that Notch activation is not required or selected for in b-catenin induced lymphomas. Thus, b-catenin activation may provide a mechanism for the induction of T-ALL that does not depend on Notch activation. Experiment Overall Design: This study was used to compare gene expression patterns of LckCre mice, CD4Cre-Ctnnbex3 mice before and after T-cell transformation. 5 independent Lckcre (control), 5 independent CD4Cre-Ctnnbex3 mice and 8 independent mice with lymphomas were used. Thymocytes or tumor masses were collected from Lckcre, CD4Cre-Ctnnbex3 mice. Total RNA isolation and purification followed by synthesis of dscDNA, Biotinylated cRNA and purification of Biotinylated cRNA. Then the hybridization to Affymetrix âMouse Expression Array 430 Genechipsâ was done. Data was analysed by dchip.
2008-06-15 | E-GEOD-7050 | biostudies-arrayexpress
Project description:Activation of b-catenin has been causatively linked to the etiology of colon cancer. Conditional stabilization of this molecule in pro-T-cells promotes thymocyte development without the requirement for preTCR signaling. We show here that activated b-catenin stalls the developmental transition from the double-positive (DP) to the single-positive (SP) thymocyte stage and predisposes DP thymocytes to transformation. b-Catenin induced thymic lymphomas have a leukemic arrest at the early DP stage. Lymphomagenesis requires Rag activity, which peaks at this developmental stage, as well as additional secondary genetic events. A consistent secondary event is the transcriptional upregulation of c-Myc, whose activity is required for transformation since its conditional ablation abrogates lymphomagenesis. In contrast, the expression of Notch receptors as well as targets is reduced in DP thymocytes with stabilized b-catenin and remains low in the lymphomas indicating that Notch activation is not required or selected for in b-catenin induced lymphomas. Thus, b-catenin activation may provide a mechanism for the induction of T-ALL that does not depend on Notch activation. Keywords: Lckcre, CD4Cre-Ctnnbex3, lymphoma, gene expression
2007-02-17 | GSE7050 | GEO
Project description:Both TCF-1 and its coactivator β-catenin are known to be required for supporting normal double positive (DP) thymocyte survival through upregulating Bcl-xL. However, the downstream factors mediating this effect remained unknown. We used microarray to compare the global expression difference among WT, TCF-1-deficient, and β-catenin transgenic thymocytes to search for the genes that are down-regulated and up-regulated in TCF-1-deficient and β-catenin transgenic thymocytes, respectively.
2011-09-01 | GSE31371 | GEO
Project description: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.
2013-06-21 | E-GEOD-48203 | biostudies-arrayexpress
Project description:Gene expression profile of Dicer knockout in mouse DP thymocytes
| PRJNA246566 | ENA
Project description:In this study, to investigate the pathogenic role of transcriptional regulator LMO2 during T lineage development, we isolated DN1, DN3, DP, CD4SP, CD8SP thymocytes, splenic CD4+ T cells and splenic CD8+ T cells from wild type and LMO2 over-expressing C57BL/6J mice for RNA-seq, and DN3 (CD25+), DP thymocytes, splenic CD4+/CD8+ T cells from transgenic mice and wild type DN3 (CD25+) thymocytes for ChIP-seq.
2023-11-01 | GSE186943 | GEO
Project description:Both TCF-1 and its coactivator β-catenin are known to be required for supporting normal double positive (DP) thymocyte survival through upregulating Bcl-xL. However, the downstream factors mediating this effect remained unknown. We used microarray to compare the global expression difference among WT, TCF-1-deficient, and β-catenin transgenic thymocytes to search for the genes that are down-regulated and up-regulated in TCF-1-deficient and β-catenin transgenic thymocytes, respectively. We focus on the genes that are significantly down-regulated and up-regulated in TCF-1-deficient and β-catenin transgenic thymocytes, respectively, to select for those genes that are potential target genes of β-catenin/TCF-1 pathway. And then those genes are subject to IPA pathway analysis searching for genes that are involved in thymocyte development and cell death.
2011-08-31 | E-GEOD-31371 | biostudies-arrayexpress
Project description:Expression data from E protein deficient double-positive (DP) thymocytes
| PRJNA121993 | ENA
Project description:The DNA binding factor Tcf-1 is one of the most prominently expressed genes in thymocytes yet its global DNA binding pattern remained unknown. Here we have assessed by ChIP-seq the Tcf-1 binding pattern in murine thymocytes in WT B6 mice and in mice expressing a stabilized form of the Tcf-1 binding partner beta-Catenin (CAT mice).
2013-06-12 | GSE46662 | GEO
Project description:We report the identification of DN NKT cells developed from DN stage thymocytes. We analyzed the gene expression profiles of NKT cells that have developed from DN stage thymocytes isolated from DP-specific E8III-Cre transgenic Rag2-floxed mouse strain, and NKT cells developed from DP thymocytes sorted as YFP-reporter positive NKT cells that were isolated from E8III-Cre transgenic Rosa26-loxP-STOP-loxP mouse.
2016-11-30 | GSE89532 | GEO