Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Expression data from WT DN3, TCF-1-deficient DN3 thymocytes, and T cell lymphomas in TCF-1-deficient animals.

ABSTRACT: TCF-1 is an HMG family transcription factor which is known to be critical for T cell development. We discovered that it has a unique role in suppressing malignant transformation of developing thymocytes at early stages. We identified ID2 and LEF-1 as key TCF-1 target genens in tumor suppression. We used microarrays to detect gene expression changes in WT and TCF-1 deficient DN3 thymocytes as well as T cell lymphoma cells developed in TCF-1 KO mice. DN3 thymocytes were directly sorted from WT or TCF-1 KO mice. T cell lymphoma blast cells were also sorted from TCF-1 KO mice that developed the disease. RNA was extracted and hybridized to GeneChip Mouse GENE 1.0 ST arrays (Affymetrix).

ORGANISM(S): Mus musculus

SUBMITTER: Hai-Hui Xue

PROVIDER: E-GEOD-33292 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

The TCF-1 and LEF-1 transcription factors have cooperative and opposing roles in T cell development and malignancy.

Yu Shuyang S Zhou Xinyuan X Steinke Farrah C FC Liu Chengyu C Chen Shann-Ching SC Zagorodna Oksana O Jing Xuefang X Yokota Yoshifumi Y Meyerholz David K DK Mullighan Charles G CG Knudson C Michael CM Zhao Dong-Mei DM Xue Hai-Hui HH

Immunity 20121025 5

The TCF-1 and LEF-1 transcription factors are known to play critical roles in normal thymocyte development. Unexpectedly, we found that TCF-1-deficient (Tcf7(-/-)) mice developed aggressive T cell malignancy, resembling human T cell acute lymphoblastic leukemia (T-ALL). LEF-1 was aberrantly upregulated in premalignant Tcf7(-/-) early thymocytes and lymphoma cells. We further demonstrated that TCF-1 directly repressed LEF-1 expression in early thymocytes and that conditional inactivation of Lef1 ...[more]

PMID: 23103132

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Project description:The thymus constitutes the primary lymphoid organ for the majority of T cells. The phosphatidyl-inositol 3 kinase (PI3K) signaling pathway is involved in lymphoid development. Defects in single components of this pathway prevent thymocytes from progressing beyond early T cell developmental stages. Protein kinase B (PKB) is the main effector of the PI3K pathway. To determine whether PKB mediates PI3K signaling in early T cell development, we characterized PKB knockout thymi. Our results reveal a significant thymic hypocellularity in PKBalpha-/- neonates and an accumulation of early thymocyte subsets in PKBalpha-/- adult mice. The latter finding is specifically attributed to the lack of PKBalpha within the lymphoid component of the thymus. Microarray analyses show that the absence of PKBalpha in early thymocyte subsets modifies the expression of genes known to be involved in pre-TCR signaling, in T cell activation, and in the transduction of interferon-mediated signals. This report highlights the specific requirements of PKBalpha for thymic development. Experiment Overall Design: Early thymocyte subsets (DN3 and ISP8) were sorted by FACS from 4 PKBalpha-/- / PKBalpha+/+ mouse littermate pairs. The same number of DN3 or ISP8 cells was sorted (7 000 to 25 000 cells) within a PKBalpha-/- / PKBalpha+/+ pair. Four replicates per condition were then analysed (4xPKBalpha-/- DN3, 4xPKBalpha+/+ DN3, 4xPKBalpha-/- ISP8, 4xPKBalpha+/+ ISP8). Total RNA was extracted using PicoPureTM RNA isolation kit (Arcturus, Sunnyvale, CA, USA) and RNA quality was controlled using the 2100 Bioanalyser (Agilent Technologies, Santa Clara, CA, USA). Total RNA was amplified and labeled using the Affymetrix 2-cycle 3â labelling kit according to manufacturerâs instructions. After fragmentation, 10 ug cRNA was hybridised to mouse genome 430 2.0 GeneChips (Affymetrix, Santa Clara, CA). The supplementary file represents the expression values estimated using the GC-RMA function provided by Refiner 3.1 (Genedata, Basel, Switzerland) for each of the samples.

Dataset Information

Expression data from WT DN3, TCF-1-deficient DN3 thymocytes, and T cell lymphomas in TCF-1-deficient animals.

Publications

The TCF-1 and LEF-1 transcription factors have cooperative and opposing roles in T cell development and malignancy.

Similar Datasets

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