Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA289878 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The transcriptional repressor Gfi1 promotes Th2 cell development and inhibits Th17 and inducible regulatory T cell differentiation. However, the contribution of Gfi1 to Th1 cell differentiation and Th1-type immune responses has not been clarified yet. We herein demonstrate that Gfi1 inhibits the activation of Th1 program in CD4 T cells. The activated Gfi1-deficient naïve CD4 T cells spontaneously develop into Th1 cells in an IL-12- and IFN-g-independent manner. The increased in vivo Th1-type immune response in Gfi1-deficient mice is confirmed using murine model of nickel allergy and delayed-type hypersensitivity. The expressions of Th1-related transcription factors including Tbx21, Eomes, Atf3, Runx1, Runx2 and Runx3 are increased in Gfi1-deficient activated CD4 T cells. Tbx21, Eomes and Runx2 are identified as candidates for direct target of Gfi1. Gfi1 binds to the Tbx21, Eomes and Runx2 gene loci and represses histone H3K4 methylation levels. Together, these findings establish a novel role of Gfi1 in inhibiting Th1 cell differentiation and Th1-type immune response.
2016-04-11 | GSE70893 | GEO
Project description:The transcriptional repressor Gfi1 promotes Th2 cell development and inhibits Th17 and inducible regulatory T cell differentiation. However, the contribution of Gfi1 to Th1 cell differentiation and Th1-type immune responses has not been clarified yet. We herein demonstrate that Gfi1 inhibits the activation of Th1 program in CD4 T cells. The activated Gfi1-deficient naïve CD4 T cells spontaneously develop into Th1 cells in an IL-12- and IFN-g-independent manner. The increased in vivo Th1-type immune response in Gfi1-deficient mice is confirmed using murine model of nickel allergy and delayed-type hypersensitivity. The expressions of Th1-related transcription factors including Tbx21, Eomes, Atf3, Runx1, Runx2 and Runx3 are increased in Gfi1-deficient activated CD4 T cells. Tbx21, Eomes and Runx2 are identified as candidates for direct target of Gfi1. Gfi1 binds to the Tbx21, Eomes and Runx2 gene loci and represses histone H3K4 methylation levels. Together, these findings establish a novel role of Gfi1 in inhibiting Th1 cell differentiation and Th1-type immune response.
2016-04-11 | GSE70829 | GEO
Project description:Investigation of whole genome gene expression level changes in Mus musculus 3B4.15 T hybridoma cells treated with 1microMolar Dexamethasone compared to mock treated cells. Interleukin-7 receptor alpha (IL-7Rα) is essential for T cell survival and differentiation. Glucocorticoids are potent enhancers of IL-7Rα expression with diverse roles in T cell biology. Here we identify the transcriptional repressor, Growth factor independent-1 (Gfi1), as a novel intermediary in glucocorticoid-induced IL-7Rα upregulation. We found Gfi1 to be a major inhibitory target of dexamethasone by microarray expression profiling of 3B4.15 T-hybridoma cells. Concordantly, retroviral transduction of Gfi1 significantly blunted IL-7Rα upregulation by dexamethasone. To further assess the role of Gfi1 in vivo, we generated bacterial artificial chromosome (BAC) transgenic mice, in which a modified Il7r locus expresses GFP to report Il7r gene transcription. By introducing this BAC reporter transgene into either Gfi1-deficient or Gfi1-transgenic mice, we document in vivo that IL-7Rα transcription is upregulated in the absence of Gfi1 and downregulated when Gfi1 is overexpressed. Strikingly, the in vivo regulatory role of Gfi1 was specific for CD8+, and not CD4+ T cells or immature thymocytes. These results identify Gfi1 as a specific transcriptional repressor of the Il7r gene in CD8 T lymphocytes in vivo. A six chip study using total RNA recovered from three separate flasks of mock treated 3B4.15 cells and three separate flasks of Dexamethasone treated 3B4.15 cells . Each chip measures the expression level of 44170 target genes
2012-07-12 | E-GEOD-39296 | biostudies-arrayexpress
Project description:Hematopoietic stem cells (HSCs) and lymphoid-primed multi-potential progenitors (LMPPs) are able to initiate both lymphoid and myeloid differentiation. We show here that the transcriptional repressor Gfi1 (growth factor independence 1) implements a specific gene expression program in HSCs and LMPPs that is critical for their survival and lymphoid differentiation potential. We present evidence that Gfi1 is required to maintain expression of genes involved in lymphoid development such as Flt-3, IL7R, Ebf1, Rag1, CCR9 and Notch1 and controls myeloid lineage commitment by regulating expression of genes such as Hoxa9 or M-CSFR. Gfi1 also inhibits apoptosis in HSCs by repressing pro-apoptotic genes such as Bax or Bak. As a consequence, Gfi1-/- mice show defects in self renewal, survival and both myeloid and lymphoid development of HSCs and LMPPs. Co-expression of a Bcl-2 transgene can partially restore the function of HSCs in Gfi1-/- mice, but not the defects in early lymphoid development. Of interest, Gfi1-/- x Bcl-2 transgenic mice show an accelerated expansion of myeloid cells and succumb to a fatal myeloproliferative disease resembling chronic myelomonocytic leukemia (CMML). Our data show that Gfi1 protects HSCs against apoptosis, ensures the proper development of LMPPs and plays a role in the development of myeloid leukemia. We used microarrays to detail the global gene expression changes following knockout of Gfi1 in mouse LSK cells We compared LSK cells isolated from Gfi1 knockout mice with wildtype cells to determine global gene expression changes by microarray analysis
2011-02-02 | E-GEOD-20282 | biostudies-arrayexpress
Project description:Double-positive (DP) thymocytes respond to intrathymic TCR signals by undergoing positive selection and lineage differentiation into single-positive (SP) mature cells. Concomitant with these wellcharacterized events is the acquisition of a mature T cell gene expression program characterized by the induction of effector molecules IL-7Ra, S1P1 and CCR7, but the underlying mechanism remains elusive. We report here that transcription repressor Gfi1 orchestrates the fidelity of DP gene expression program and developmental maturation into SP cells. Loss of Gfi1 resulted in premature induction of effector genes and transcription factors Foxo1 and Klf2 in DP thymocytes, and accumulation of post-selection intermediate populations and accelerated transition into SP cells. Strikingly, partial loss of Foxo1 function, but not restored survival fitness, rectified the dysregulated gene expression and thymocyte maturation in Gfi1-deficient mice. Our results establish Gfi1-Foxo1 axis and the transcriptional circuitry that actively maintain DP identity and shape the proper generation of mature T cells
2016-12-19 | GSE89898 | GEO
Project description:CD4 T cells were activated using CD3/CD28 antibodies in the presence of IL2 and IL12, to generate Th1 cells. Th1 cells were maintained and expanded in IL2 and IL12, on D5 Th1 cells were sorted for CD4+ expression and DAP1 exclusion. After flow sorting, live TH1 cells were resuspended (1e6 per ml) in methionine free RPMI, supplemented with 10% dialysed FBS, IL2 and IL12, and with L-methionine (100μM, or 1μM). Cells were cultured for 5 hrs before collection for proteomics processing.
2019-03-29 | PXD012053 | Pride
Project description:This study provides evidence on the molecular mechanisms by which P2RX7 signaling promotes Th1 cell differentiation. P2RX7 induces T-bet expression and aerobic glycolysis in splenic CD4+ T cells that respond to malaria, at a time prior to Th1/Tfh polarization. Cell-intrinsic P2RX7 signaling sustains the glycolytic pathway and causes bioenergetic mitochondrial stress in activated CD4+ T cells. We also show in vitro the phenotypic similarities of Th1-polarized CD4+ T cells that do not express P2RX7 and those in which the glycolytic pathway is pharmacologically inhibited. In addition, ATP synthase blockade in vitro and the consequent inhibition of oxidative phosphorylation, which forces cells to use aerobic glycolysis, is sufficient to promote rapid CD4+ T cell proliferation and polarization to the Th1 profile in the absence of P2RX7. These data demonstrate that P2RX7-mediated metabolic reprograming for aerobic glycolysis is a key event for Th1 cell differentiation and suggest that ATP synthase inhibition is a fundamental mechanism by which P2X7 signaling induces the Th1 response.
2023-03-08 | PXD037754 | Pride
Project description:In immune responses, activated T cells migrate to B cell follicles and develop to T follicular helper (Tfh) cells, a new subset of CD4+ T cells specialized in providing help to B lymphocytes in the induction of germinal centers 1-3. Although Bcl6 has been shown to be essential in Tfh cell function, it may not regulate the initial migration of T cells 4 or the induction of Tfh program as exampled by CXCR5 upregulation 5. Here, we show that the Achaete-Scute homologue 2 (Ascl2) gene that encodes a basic helix-loop-helix (bHLH) transcription factor 6, is selectively upregulated in its expression in Tfh cells. Ectopic expression of Ascl2 uniquely upregulates CXCR5 but not Bcl6 and downregulates CCR7 expression in T cells in vitro and accelerates T cell migration to the follicles and Tfh cell development in vivo. Combined transcriptome profiling and genome-wide occupancy analysis indicate that Ascl2 directly regulates Tfh-related genes while inhibits expression of Th1 and Th17 genes. Acute deletion of Ascl2 as well as blockade of its function with the Id3 protein in peripheral CD4+ T cells results in a failure in Tfh cell development and the germinal center response. Conversely, mutation of Id3, known to cause antibody-mediated autoimmunity, greatly enhances Tfh cell generation. Thus, Ascl2 critically and directly initiates Tfh cell development. Decide Ascl2 binding sites in CD4+ T cells
2014-01-01 | E-GEOD-52839 | biostudies-arrayexpress
Project description:Investigation of whole genome gene expression level changes in Mus musculus 3B4.15 T hybridoma cells treated with 1microMolar Dexamethasone compared to mock treated cells. Interleukin-7 receptor alpha (IL-7Rα) is essential for T cell survival and differentiation. Glucocorticoids are potent enhancers of IL-7Rα expression with diverse roles in T cell biology. Here we identify the transcriptional repressor, Growth factor independent-1 (Gfi1), as a novel intermediary in glucocorticoid-induced IL-7Rα upregulation. We found Gfi1 to be a major inhibitory target of dexamethasone by microarray expression profiling of 3B4.15 T-hybridoma cells. Concordantly, retroviral transduction of Gfi1 significantly blunted IL-7Rα upregulation by dexamethasone. To further assess the role of Gfi1 in vivo, we generated bacterial artificial chromosome (BAC) transgenic mice, in which a modified Il7r locus expresses GFP to report Il7r gene transcription. By introducing this BAC reporter transgene into either Gfi1-deficient or Gfi1-transgenic mice, we document in vivo that IL-7Rα transcription is upregulated in the absence of Gfi1 and downregulated when Gfi1 is overexpressed. Strikingly, the in vivo regulatory role of Gfi1 was specific for CD8+, and not CD4+ T cells or immature thymocytes. These results identify Gfi1 as a specific transcriptional repressor of the Il7r gene in CD8 T lymphocytes in vivo.
2012-07-13 | GSE39296 | GEO
Project description:GFI is a DNA binding transcriptional repressor that regulates myeloid differentiation. Here, we show that GFI1 interacts with the chromodomain helicase CHD4 and other components of the nucleosome remodeling and deacetylase (NuRD) complex. Our data demonstrated that GFI1 and GFI1/CHD4 complexes occupy sites of open chromatin enriched for histone marks associated with active transcription or different sets of genes that are either enriched for IRF1 or SPI-1 consensus binding sites. In addition, our study provided evidence that GFI1 affects the chromatin remodeling activity of the NuRD complex. Overall, our results indicate that GFI1/CHD4 complexes control chromatin openness and histone modifications differentially to regulate target genes, which govern the immune response, nucleosome organization, or metabolic processes.
2021-11-02 | PXD028945 | Pride