Ectopic Tcf1 expression reprograms exhausted CD8+ T cells to acquire stem cell-like features [ATAC-seq]
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PROVIDER: PRJNA578114 | ENA |
REPOSITORIES: ENA
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Project description:Ectopic Tcf1 expression reprograms exhausted CD8+ T cells to acquire stem cell-like features
| PRJNA578159 | ENA
Project description:The goal of this study is to determine the capacity of Tcf1 to reprogram exhausted CD8+ T cells for function restoration. Tex cells elicited by chronic infection contain a CXCR5+Tim3– subset that has stem cell-like self-renewing capacity and expresses an elevated level of Tcf1 (termed Tex-stem), and Tex-stem cells depend on Tcf1 for generation and persistence. We show that ectopic Tcf1 expression profoundly affected the transcriptome of Tex cells.
2020-04-30 | GSE139057 | GEO
Project description:The goal of this study is to determine the capacity of Tcf1 to reprogram exhausted CD8+ T cells for function restoration. Tex cells elicited by chronic infection contain a CXCR5+Tim3– subset that has stem cell-like self-renewing capacity and expresses an elevated level of Tcf1 (termed Tex-stem), and Tex-stem cells depend on Tcf1 for generation and persistence. We show that ectopic Tcf1 expression profoundly affected the chromatin accessibility of Tex cells.
2020-04-30 | GSE139024 | GEO
Project description:The goal of this study is to determine the capacity of Tcf1 to reprogram exhausted CD8+ T cells for function restoration. Tex cells elicited by chronic infection contain a CXCR5+Tim3– subset that has stem cell-like self-renewing capacity and expresses an elevated level of Tcf1 (termed Tex-stem), and Tex-stem cells depend on Tcf1 for generation and persistence. We show that ectopic Tcf1 expression profoundly affected the transcriptome and chromatin accessibility of Tex cells.
2020-04-30 | GSE139056 | GEO
Project description:Ectopic Tcf1 expression reprograms exhausted CD8+ T cells to acquire stem cell-like features [CUT&RUN]
| PRJNA578160 | ENA
Project description:Ectopic Tcf1 expression reprograms exhausted CD8+ T cells to acquire stem cell-like features [RNA-seq]
| PRJNA578161 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-04-30 | GSE139058 | 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: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.
2011-08-03 | E-GEOD-26559 | biostudies-arrayexpress
Project description:We used microarrays to perform a global gene expression analysis in Tcf1-expressing Thy1+CD25+ T lineage cells that develop on OP9 stroma in the absence of Notch1 signals. We compare this to the starting population, LMPP progenitors, and to control expressing T lineage cells that developed on OP9 stroma expressing Notch ligand DL4. The overall goal of this study was to determine if Tcf1 initiates T lineage specification in lymphoid progenitors. We found that Tcf1 was sufficient to upregulate many T lineage genes as compared to control expressing progenitors on OP9-DL4. 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. Wiltype LMPPs were isolated by a FACSAria cell sorter and retrovirally transduced with a Tcf1-containing (Tcf1-VEX) or control vector (VEX) retrovirus. Tcf1-expressing cells and control-vector expressing cells were then seeded on OP9 stroma or OP9 stroma expressing Notch ligand DL4, respectively. On day 10, Thy1+CD25+ T lineage cells were sorted from Tcf1-expressing cells on OP9 stroma and compared to sorted LMPPs and Thy1+CD25+ T lineage cells that developed from control-vector expressing cells on OP9-DL4.
2011-08-03 | E-GEOD-26560 | biostudies-arrayexpress