Tcf-1 expression in murine thymus
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE46662 | GEO | 2013/06/12
SECONDARY ACCESSION(S): PRJNA201421
REPOSITORIES: GEO
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Project description:The DNA binding factor Tcf-1 is one of the most prominently expressed genes in thymocytes yet it's global DNA binding pattern remained unknown. Here we have assessed by ChIP-seq the Tcf-1 binding pattern in murine thymocytes. Tcf-1 ChIP-seq of 1 sample and input control.
2013-06-12 | E-GEOD-46662 | biostudies-arrayexpress
Project description: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).
2012-10-25 | E-GEOD-33292 | biostudies-arrayexpress
Project description: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.
2012-10-25 | GSE33292 | GEO
Project description:Comparison of wild-type and Tcf-1-deficient DN3 thymocytes
2021-11-01 | GSE93346 | 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: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:The HMG-box factor Tcf1 is required during T-cell development in the thymus and mediates the nuclear response to Wnt signals. Tcf1-/- mice have previously been characterized and show developmental blocks at the CD4-CD8- double negative (DN) to CD4+CD8+ double positive transition. Due to the blocks in T-cell development, Tcf1-/- mice normally have a very small thymus. Unexpectedly, a large proportion of Tcf1-/- mice spontaneously develop thymic lymphomas with 50% of mice developing a thymic lymphoma/leukemia at the age of 16 wk. These lymphomas are clonal, highly metastatic, and paradoxically show high Wnt signaling when crossed with Wnt reporter mice and have high expression of Wnt target genes Lef1 and Axin2. In wild-type thymocytes, Tcf1 is higher expressed than Lef1, with a predominance of Wnt inhibitory isoforms. Loss of Tcf1 as repressor of Lef1 leads to high Wnt activity and is the initiating event in lymphoma development, which is exacerbated by activating Notch1 mutations. Thus, Notch1 and loss of Tcf1 functionally act as collaborating oncogenic events. Tcf1 deficiency predisposes to the development of thymic lymphomas by ectopic up-regulation of Lef1 due to lack of Tcf1 repressive isoforms and frequently by cooperating activating mutations in Notch1. Tcf1 therefore functions as a T-cell‚Äìspecific tumor suppressor gene, besides its established role as a Wnt responsive transcription factor. Thus, Tcf1 acts as a molecular switch between proliferative and repressive signals during T-lymphocyte development in the thymus. Using the Tcf1-/- DeltaVII/DeltaVII knockout mouse (Verbeek et al. Nature 1995), thymocytes of 17 mice (5 control Tcf+/-, 4 Tcf-/- and 8 Tcf-/- with thymic lymphoma) were homogenized for RNA isolation using Qiagen RNeasy minicolumns. The quantity and quality of total RNA was determined using spectrophotometry (Nanodrop) and an Agilent Bioanalyzer. One ¬µg of RNA was used to generate cRNA using Affymetrix One cycle cDNA synthesis kit (Affymetrix, Santa Clara, CA, USA), after which the samples were biotinylated using an Affymetrix IVT labeling kit (Affymetrix). The samples were hybridized overnight at 42¬?C to GeneChip mouse genome 430 2.0 Arrays (Affymetrix). Washing and staining steps were performed on a Fluidics station 450, and the Genechips were scanned using a GeneChip scanner 3000 (Affymetrix) at the Department of Immunology, Erasmus Medical Center. Raw data were normalized and summarized using Robust Multichip Average (RMA) method. The experiment consists of 5 control Tcf+/- thymi, 4 Tcf-/- thymi and 8 Tcf-/- thymus samples with thymic lymphoma.
2014-02-14 | E-GEOD-54976 | biostudies-arrayexpress
Project description:In development, pioneer transcription factors access silent chromatin to reveal lineage-specific gene programs. The structured DNA-binding domains of pioneer factors have been well characterized, but whether and how low-complexity intrinsically disordered regions (IDRs) affect chromatin and control cell fate is unclear. Here, we report deletion of an IDR of the pioneer factor TCF-1, termed “L1”, leads to an early developmental block in T cells. The few T cells that develop from progenitors expressing TCF-1 lacking L1 exhibit lineage infidelity distinct from the lineage diversion of TCF-1 deficient cells. Mechanistically, L1 is required for activation of T cell genes and de-repression of GATA2 driven genes, normally reserved to the mast cell and dendritic cell lineages. Underlying this lineage diversion, L1 mediates binding of TCF-1 to its earliest target genes which are subject to repression as T cells develop. These data suggest TCF-1’s intrinsically disordered N-terminus maintains T cell lineage fidelity.
2024-06-16 | PXD043586 | Pride
Project description:ab and gd T cells originate from a common, multi-potential precursor population in the thymus, but the molecular mechanisms regulating this lineage fate decision process are unknown. We have identified Sox13 as a gd-specific gene in the immune system. Using Sox13 transgenic mice, we show that SOX13 promotes gd T cell development while opposing ab T cell differentiation. Conversely, mice deficient in Sox13 expression exhibited impaired development of gd T cells, but not ab T cells. One mechanism of SOX13 function is the inhibition of WNT/TCF signaling, suggesting that differential WNT/TCF activity is an essential parameter for this binary cell fate choice. Experiment Overall Design: CD4+CD8+ double positive thymocyte subsets were sorted by FACS using total pooled thymocytes from minimum of two mice and immediately lysed in Trizol. Comparison groups in each experiment were DP thymocytes from Sox13 transgenic mice and wild type B6 littermate controls. Gene expression profiling was performed according to the manufacturerâ??s protocol (Affymetrix). Labeled cRNA (from total RNA) was generated and applied to Affymetrix Mu11K(A and B) (expt 1) or muU74Av2 (expt 2) microarrays. Results were analyzed using Microarray Analysis Software v4 and v5 (Affymetrix).
2008-06-14 | E-GEOD-6311 | biostudies-arrayexpress
Project description:Lineage-determine transcription factors (LDTFs) can determine gene expression programs of a specific cell type, by rewiring the linear regulatory network. However, it’s not clear whether and how LDTFs can alter the 3D genome organization during development. Here, we investigated the effect of T cell factor 1 (TCF-1) on the reconfiguration of 3D genome during T cell development. Topologically associated domains (TADs) that have higher density of TCF-1 gain more intra-TAD interactions during T cell development. TCF-1 colocalized with CCCTC-binding factor (CTCF) substantially reduced the insulation and increased the local interactions, which additionally have stronger interactions with T cell development genes. We further found that a considerable number of boundaries are lost during T cell development, and that TCF-1 is enriched at the lost boundaries, including the ones near key T cell development genes. Overexpression of TCF-1 in fibroblast demonstrates that both high density of TCF-1 and TCF-1 colocalized with CTCF can optimally increase the local interactions. Correspondingly, knocking out of TCF-1 in DN3 cell line leads to decreased intra-TAD interactions and gain of insulation at some of its binding sites. Finally, we found that TCF-1 can recruit and maintain cohesin at its binding sites, which probably cause reconfiguration of the 3D genome. Taken together, our study shows that TCF-1 can change the 3D genome at both TAD level and finer scale potentially through the recruitment of cohesin.
2022-05-02 | GSE178344 | GEO