Analysis of gene expression sigunature in Utx KO CD8 T cells
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PROVIDER: PRJNA886661 | ENA |
REPOSITORIES: ENA
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Project description:To elucidate the effect of Utx, histone demethylase, on CD8 Tcell diferentiation, The gene expression were measured in WT and Utx KO CD8 T cells.
2023-07-12 | GSE214673 | GEO
Project description:Although the methylation status of histone H3K27 plays a critical role in CD4+ T cell differentiation and its function, the role of Utx, histone H3K27 demethylase, in the CD8+ T cell-dependent immune response remains unclear. We therefore generated T cell-specific Utx knockout (Utx KO) mice to determine the role of Utx in CD8+ T cells. Wild-type (WT) and Utx KO mice were infected with Listeria monocytogenes expressing OVA to analyze the immune response of Ag-specific CD8+ T cells upon primary and secondary infections. There was no significant differences in the primary expansion of Ag-specific CD8+ T cells between WT and Utx KO mice. However, Utx deficiency resulted in an increased secondary expansion of Ag-specific CD8+ T cells. Adoptive transferred Utx KO CD8+ T cells resulted in increased numbers of CD127hi KLRG1lo memory precursors in the primary expansion and larger numbers of memory cells. We observed a decreased gene expression of effector-associated transcription factors, including Prdm1 encoding Blimp1, in Utx KO CD8+ T cells upon primary infection. We confirmed that the tri-methylation level of histone H3K27 in the Prdm1 gene loci in the Utx KO cells was higher than in the WT cells. The treatment of CD8+ T cells with Utx-cofactor α-ketoglutarate hampered the memory formation, while Utx-inhibitor GSK-J4 enhanced the memory formation and increased the secondary expansion in WT CD8+ T cells. These data suggest that Utx negatively controls the memory formation of Ag-stimulated CD8+ T cells by epigenetically regulating the expression of genes, including Prdm1. Based on these findings, we identified a critical link between Utx and the differentiation of Ag-stimulated CD8+ T cells upon infection
2021-08-31 | GSE119312 | GEO
Project description:Single-cell RNA-seq - Jmj KO, Utx KO, Tdt.Control
| PRJNA776255 | ENA
Project description:Immunoprecipitation of Utx followed by mass spectrometry analysis to identify Utx binding partners in mouse myeloid progenitor cells.
2018-04-30 | PXD005011 | Pride
Project description:Persistent virus infections can cause pathogenesis that is debilitating or lethal. During these infections, virus-specific T cells fail to protect due to weakened antiviral activity or failure to persist. These outcomes are governed epigenetically, though it is unknown which enzymes contribute to T cell loss or impaired function over time. Here, we show that T cell receptor-stimulated CD8+ T cells increase their expression of UTX (Ubiquitously transcribed Tetratricopeptide repeat, X-chromosome), an enzyme involved in demethylating histone-3 lysine-27 (H3K27), and reduce genome-wide H3K27-me3. UTX limits the frequency and durability of virus-specific CD8+ T cells during chronic lymphocytic choriomeningitis virus (LCMV) infection in mice by promoting inhibitory receptor expression and apoptosis. UTX also increases effector gene expression to improve CTL-mediated protection, a process corresponding to reduced H3K27me3 at effector gene bodies. Thus, UTX guides gene expression patterns in CD8+ T cells, promoting antiviral activity while reducing CD8+ T cell durability.
2021-02-09 | GSE143736 | GEO
Project description:The goal of this study was to examine differences in gene expression of tumor specific CD8 T cells in an in vivo tumor mouse model after inhibition of galectin-3 protein expression by genetic knockout. Galectin-3 is thought to modulate CD8 T cell response by cross-linking cell surface glycoproteins Galectin-3 is a 31 kD carbohydrate-binding lectin that is over-expressed by many human malignancies. It also modulates T cell responses through a diverse array of mechanisms including induction of apoptosis, TCR cross linking in CD8+ T cells, and T cell receptor (TCR) down regulation in CD4+ T cells. We found that patients responding to a granulocyte-macrophage colony-stimulating factor (GM-CSF) secreting allogeneic pancreatic tumor vaccine developed post immunization antibody responses to galectin-3 on a proteomic screen. We used the HER-2/neu (neu-N) transgenic mouse model to study galectin-3 binding on adoptively transferred high avidity neu-specific CD8+ T cells derived from TCR transgenic mice. Here, we show that galectin-3 binds preferentially to activated antigen-committed CD8+ T cells only in the tumor microenvironment (TME). Galectin-3 deficient mice exhibit improved CD8+ T cell effector function and increased expression of several inflammatory genes when compared with wild type (WT) mice. We also show that galectin-3 binds to LAG-3, and LAG-3 expression is necessary for galectin-3 mediated suppression of CD8+ T cells in vitro. Lastly, galectin-3 deficient mice have significantly elevated levels of circulating plasmacytoid dendritic cells (pDCs), which are superior to conventional dendritic cells (cDCs) in activating CD8+ T cells. Binding of galectin-3 to cell-surface glycoproteins on immune cells suppresses a pro-inflammatory immune response. Thus, inhibiting galectin-3 in conjunction with CD8+ T cell directed immunotherapies should enhance the tumor specific immune response. 3 different experimental groups were studied. Galectin-3 WT CD8 T cells adoptively transferred into Galectin-3 WT mice, galectin-3 WT CD8 T cells transferred into galectin-3 KO mice, and finally galectin-3 KO CD8 T cells transferred into galectin-3 KO mice. Galectin-3 WT CD8 T cells transferred into Galectin-3 WT mice were used as the reference group. Four biological replicates were submitted for each group, and adoptively transfered CD8 T cells were isolated 5 days post-adoptive transfer into tumor-bearing mice treated with a whole cell GM-CSF secreting vaccine. Cells were purified by cell sorting on the Thy1.2 surface marker.
2015-02-19 | E-GEOD-59454 | biostudies-arrayexpress
Project description:UTX gene is localized on the X chromosome, identified as a demethylase on histone H3 lysine 27. Two independent UTX conditional knockout (cKO) embryonic stem cell lines and two UTX knockout (KO) cell lines were cultured on 0.1% gelatin-coated dishes without feeder cells at desity of 1 million cells/10 cm dish. Cells were cultured overnight and collected. Total RNAs were sequentially purified with Trizol (Invitrogen) and RNeasy kit (Qiagen) and analyzed on Mouse Genome 430 2.0 Array (Affymetrix) at NIDDK Microarray Core Facility following standard protocols.
2012-09-04 | E-GEOD-35415 | biostudies-arrayexpress
Project description:To elucidate the effect of menin on the differentiation of CD8 T cell, the gene expression were measured in WT and Menin KO CD8 T cells.
2023-07-12 | GSE215391 | GEO
Project description:Hematopoitic stem cells from Utx/p53 DKO mice showed increased self-renewal potential and predisposition of differentiation to myeloid lineage compared with those from p53 KO mice. To figure out what mechanism leads to the increased self-renewal, we compared the transcriptional profiles using RNA-sequencing of FACS sorted LSK (Lin-Ckit+Sca1+) cells, which contains the hematopoietic stem cells.
2018-10-08 | GSE97737 | GEO
Project description:The biological functions of histone demethylases Jmjd3 and Utx remain poorly understood. We assessed such functions in developing T cells, using conditional (CD4-Cre-mediated) gene disruption, by inactivating Kdm6a and Kdm6b, respectively encoding Utx and Jmjd3, in immature CD4+CD8+ thymocytes. We compared microarray gene expression in mature (Va2hi CD24lo) mutant and wild-type CD4+CD8- thymocytes carrying the OT-II TCR transgene. We show that Jmjd3 and Utx redundantly promote H3K27Me3 removal at, and expression of, a specific subset of genes involved in terminal thymocyte differentiation, especially S1pr1, encoding a sphingosine-phosphate receptor required for thymocyte egress. Mature (Va2hi CD24lo) CD4 thymocytes were sorted from freshly prepared single-cell suspensions OT-II TCR transgenic thymocytes deficient for Utx and Jmjd3 (dKO, CD4-Cre conditional deletion of floxed Kdm6a and Kdm6b alleles), and from Cre-negative controls (wild-type). Total RNA was extracted from sorted thymocytes using the RNeasy Plus Mini Kit (Qiagen) and processed for microarray analyses (Affymetrix Mouse Exon 1.0 ST array) at the NCI microarray facility, following the manufacturer’s recommendation. Data is generated from 3 replicates from each experiment.
2015-09-17 | E-GEOD-70363 | biostudies-arrayexpress