Tcf1 and Lef1 establish CD8+ T cell identity via their intrinsic histone deacetylase activity
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Hai-Hui Xue
PROVIDER: E-GEOD-73240 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Comparison of epigenome and Tcf1 occupancy between control and Tcf1/Lef1-deficient CD8 T cells Control mice or those are deficient for Tcf1 and Lef1 transcription factors (deleted by CD4-Cre) were used to isolate thymocytes. The thymocytes were surface-stained to identify TCRbeta high, CD69â, CD24â CD8+ subsets. These cells were sorted for ChIPseq analysis of various histone marks. Control mice or those are deficient for Tcf1 (deleted by CD4-Cre) were used to isolate thymocytes. The splenocytes were surface-stained to identify TCRbeta high, CD8+ subsets. These cells were sorted for ChIPseq analysis of Tcf1 binding locations.
2016-02-12 | E-GEOD-73239 | biostudies-arrayexpress
Project description:Comparison of transcriptome between control and Tcf1/Lef1-deficient mature CD8 thymocytes Control mice or those are deficient for Tcf1 and Lef1 transcription factors (deleted by CD4-Cre) were used to isolate thymocytes. The thymocytes were surface-stained to identify TCRbeta high, CD69â, CD24â CD8+ subsets. These cells were sorted for RNAseq analysis.
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Project description:Generation of transcriptomes to provide in-depth expression profiles of tTreg and tTconv and to obtain the differential expression signature defining thymic Tregs in humans.
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2007-05-23 | E-MEXP-755 | biostudies-arrayexpress
Project description:We mapped genome-wide Tcf1 binding locations in mature CD8 T cells to identify its direct target genes. This experiment aims to identify genome-wide binding locations for Tcf1 transcription factor in mature CD8 T cells. The CD8 T cells were isolated from wild-type C57BL/6 mice by negative selection. The chromatin fragments were immunoprecipitated by an anti-Tcf1 antiserum or control rabbit serum (without immunization). The immunoprecipitated fragments were then used in high throughput sequencing. Data processing then revealed >3000 high-confidence Tcf1 binding peaks across the CD8 T cell genome. One important finding is that Tcf1 binds directly to Cd4 gene silencer, and thus explain its important role in suppressing the CD4 coreceptor in mature CD8 T cells.
2014-03-05 | E-GEOD-52070 | biostudies-arrayexpress
Project description:CD8SP TCRhi thymocytes were sorted from TNFR1-/- and TNFR1-/- CD4Cre+ IKK1fx/fx IKK2fx/fx R26REYFPfx/fx mice. RNA was produced from the sorted cells and sequencing performed. Samples 1,2 and 3 were from TNFR1-/- mice Samples 4, 5, 6 and 7 were from TNFR1-/- CD4Cre+ IKK1fx/fx IKK2fx/fx R26REYFPfx/fx mice
2017-07-05 | E-MTAB-4778 | biostudies-arrayexpress
Project description:Genetic studies in T-cell acute lymphoblastic leukemia have uncovered a remarkable complexity of oncogenic and loss-of-function mutations. Amongst this plethora of genetic changes, NOTCH1 activating mutations stand out as the most frequently occurring genetic defect, identified in more than 50% of T-cell acute lymphoblastic leukemias, supporting an essential driver role for this gene in T-cell acute lymphoblastic leukemia oncogenesis. In this study, we aimed to establish a comprehensive compendium of the long non-coding RNA transcriptome under control of Notch signaling. For this purpose, we measured the transcriptional response of all protein coding genes and long non-coding RNAs upon pharmacological Notch inhibition in the human T-cell acute lymphoblastic leukemia cell line CUTLL1 using RNA-sequencing. Similar Notch dependent profiles were established for normal human CD34+ thymic T-cell progenitors exposed to Notch signaling activity in vivo. In addition, we generated long non-coding RNA expression profiles (array data) from GSI treated T-ALL cell lines, ex vivo isolated Notch active CD34+ and Notch inactive CD4+CD8+ thymocytes and from a primary cohort of 15 T-cell acute lymphoblastic leukemia patients with known NOTCH1 mutation status. Integration of these expression datasets with publically available Notch1 ChIP-sequencing data resulted in the identification of long non-coding RNAs directly regulated by Notch activity in normal and malignant T-cell context. Given the central role of Notch in T-cell acute lymphoblastic leukemia oncogenesis, these data pave the way towards development of novel therapeutic strategies that target hyperactive Notch1 signaling in human T-cell acute lymphoblastic leukemia. Gene expression was measured in sorted T-cell subsets of 4 healthy donors.
2014-10-27 | E-GEOD-61873 | biostudies-arrayexpress
Project description:We aimed to identify miRNAs and pathways specifically deregulated in adolescent and young adult (AYA) T-ALL patients. Small RNA-seq showed no major differences between AYA and pediatric T-ALL, but it revealed downregulation of miR-143-3p in T-ALL patients. Prediction algorithms identified several known and putative oncogenes targeted by this miRNA, including KRAS, FGF1, and FGF9. Pathway analysis indicated signaling pathways related to cell growth and proliferation, including FGFR signaling and PI3K-AKT signaling, with the majority of genes overrepresented in these pathways being predicted targets of hsa-miR-143-3p. By luciferase reporter assays, we validated direct interactions of this miRNA with KRAS, FGF1 and FGF9. In cell proliferation assays, we showed reduction of cell growth upon miR-143-3p overexpression in two T-ALL cell lines. Our study is the first description of the miRNA transcriptome in AYA T-ALL patients and the first report on tumor suppressor potential of miR-143-3p in T-ALL. Downregulation of this miRNA in T-ALL patients might contribute to enhanced growth and viability of leukemic cells. We also discuss the potential role of miR-143-3p in FGFR signaling. Although this requires more extensive validation, it might be an interesting direction, since FGFR inhibition proved promising in preclinical studies in various cancers.
2022-09-06 | E-MTAB-11987 | biostudies-arrayexpress
Project description:Tcf1 is necessary for optimal T lineage development. Tcf1 deficient progenitors fail to initiate the T lineage program in vitro and development is severely defective in vivo. We used microarrays to assess the overal global gene expression differences from Tcf1 wildtype and deficient lymphoid biased progenitors cultures on Notch-ligand expressing stroma to determine if Tcf1 deficient progenitors are able to intiate the T lineage specification program. Abstract of manuscript: The thymus imposes the T cell fate on incoming multipotent progenitors, but the molecular mechanisms are poorly understood. We show that transcription factor Tcf1 initiates T-lineage-specific gene expression. Tcf1 is downstream of Notch1 signaling and expressed in early T-cell progenitors. Progenitors deficient for Tcf1 are unable to initiate normal T-lineage specification. Conversely, ectopic expression of Tcf1 in hematopoietic progenitors is sufficient to induce expression of T-lineage specific genes in vitro. Thus, our study identifies Tcf1 as critically involved in the establishment T cell identity. Tcf1 wildtype and deficient bone marrow lymphoid primed progenitors (LMPPs, Lineage marker- Sca+kit+Flt3high) were harvested in triplicate and seeded onto OP9-DL4 expressing stroma for 4 days upon which highly pure lineage negative and Thy1+CD25+ T cells were cell sorted for expression analysis. The lineage negative populations represent three seperate mice from each genotype and the Thy1+CD25+T lineage population represents two replicates from the Tcf1 wildtype group. No Thy1+CD25+ T lineage cells develop from Tcf1 deficient progentiors.
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Project description:Here we developed CapStarr-Seq, a novel high-throughput strategy to quantitatively assess enhancer activity in mammals. This approach couples capture of regions of interest to previously developed Starr-seq technique. Extensive assessment of CapStarr-seq demonstrated accurate quantification of enhancer activity. Furthermore, we found that enhancer strength correlates with binding complexity of tissue-specific transcription factors and super-enhancers, while additive enhancer activity isolates key genes involved in cell identity and function. ChIP-seq for the transcription factors HEB and TCF1, the DNaseI and the epigenetic modification H3K9me3 in DP thymocytes.
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