Expression data comparing PLZF+/+, PLZF +/lu, PLZF lu/lu gammadelta NKT cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Michael Gleimer
PROVIDER: E-GEOD-42168 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Natural killer (NKT) T cells exhibit tissue distribution, surface phenotype, and functional responses that are strikingly different from those of conventional T cells. The transcription factor PLZF is responsible for most of these properties, as its ectopic expression in conventional T cells is sufficient to confer to them an NKT-like phenotype. The molecular program downstream of PLZF, however, is largely unexplored. Here we report that PLZF regulates the expression of a surprisingly small set of genes, many with known immune functions. This includes several established components of the NKT cell developmental program.
2012-11-09 | GSE42168 | GEO
Project description:The transcription factor PLZF (promyelocytic leukemia zinc finger) is encoded by the BTB domain-containing 16 (Zbtb16) gene. Its repressor function regulates specific transcriptional programs. During the development of invariant natural killer T (NKT) cells, PLZF is expressed and directs their effector program but the detailed mechanisms underlying PLZF regulation of multi-stage NKT cell developmental program are not well understood. This study investigated the role of acetylation-induced PLZF activation on NKT cell development by analyzing mice expressing a mutant form of PLZF mimicking constitutive acetylation (PLZFON mice). NKT populations in PLZFON mice were reduced in proportion and numbers of cells, and the cells present were blocked at the transition from developmental stage 1 to stage 2. NKT cell subset differentiation was also altered, with T-bet+ NKT1 and RORt+ NKT17 subsets dramatically reduced, and the emergence of a T-bet-RORt- NKT cell subset with features of cells in early developmental stages rather than mature NKT2 cells. Preliminary analysis of DNA methylation patterns suggested that activated PLZF acts on the DNA methylation signature to regulate NKT cells’ entry into the early stages of development, while repressing maturation. In wild-type NKT cells, deacetylation of PLZF is possible, allowing subsequent NKT cell differentiation. Interestingly, development of other innate lymphoid and myeloid cells, that are dependent on PLZF for their generation, is not altered in PLZFON mice highlighting lineage specific regulation. Overall, we propose that specific epigenetic control of PLZF through acetylation levels is required to regulate normal NKT cell differentiation. Key points: Constitutive acetylation of PLZF (PLZFON) blocks NKT cell development. PLZFON might act on the DNA methylation signature to control gene expression. PLZF acetylation levels regulate normal NKT cell differentiation.
2021-05-24 | GSE128558 | GEO
Project description:The transcription factor PLZF (promyelocytic leukemia zinc finger) is encoded by the BTB 42 domain-containing 16 (Zbtb16) gene. Its repressor function regulates specific transcriptional 43 programs. During the development of invariant natural killer T (NKT) cells, PLZF is 44 expressed and directs their effector program but the detailed mechanisms underlying PLZF 45 regulation of multi-stage NKT cell developmental program are not well understood. This 46 study investigated the role of acetylation-induced PLZF activation on NKT cell development 47 by analyzing mice expressing a mutant form of PLZF mimicking constitutive acetylation (PLZFON mice). NKT populations in PLZFON 48 mice were reduced in proportion and numbers 49 of cells, and the cells present were blocked at the transition from developmental stage 1 to stage 2. NKT cell subset differentiation was also altered, with T-bet+ NKT1 and RORJt + 50 NKT17 subsets dramatically reduced, and the emergence of a T-bet - RORJt - 51 NKT cell subset 52 with features of cells in early developmental stages rather than mature NKT2 cells. Analysis 53 of DNA methylation patterns indicated that activated PLZF establishes a unique DNA 54 methylation signature to regulate NKT cells’ entry into the early stages of development, while 55 repressing maturation. In wild-type NKT cells, deacetylation of PLZF alleviates this 56 repression and allows subsequent NKT cell differentiation. Interestingly, development of 57 other innate lymphoid and myeloid cells, that are dependent on PLZF for their generation, is not altered in PLZFON 58 mice highlighting lineage specific regulation. Overall, we propose that 59 specific epigenetic control of PLZF through acetylation levels is required to regulate normal 60 NKT cell differentiation.
2021-04-21 | GSE171984 | GEO
Project description:To identify genes that require PLZF for their regulation in NKT cells, we compared the developmental stages of thymic NKT cells from wildtype and PLZF-deficient mice The transcription factor PLZF is induced during the development of innate and innate-like lymphocytes to direct their acquisition of a T helper effector program, but the molecular mechanisms involved are poorly understood. Using biotinylation-based ChIP-seq and microarray analysis of both NKT and PLZF-transgenic thymocytes, we identified several layers of regulation of the innate-like NKT effector program: first, PLZF bound and regulated genes encoding cytokine receptors as well as homing and adhesion receptors; second, PLZF bound and activated T helper-specific transcription factor genes that in turn control T helper specific programs; finally, PLZF bound and suppressed the transcription of Bach2, a potent general repressor of effector differentiation in naive T cells. These findings reveal the architecture of the transcriptional program recruited by PLZF and elucidate how a single transcription factor can drive the developmental acquisition of a broad effector program.
2016-05-24 | GSE81771 | GEO
Project description:Using biotinylation-based ChIP-seq and microarray analysis of both NKT and PLZF-transgenic thymocytes, we identified several layers of regulation of the innate-like NKT effector program. The transcription factor PLZF is induced during the development of innate and innate-like lymphocytes to direct their acquisition of a T helper effector program, but the molecular mechanisms involved are poorly understood. Using biotinylation-based ChIP-seq and microarray analysis of both NKT and PLZF-transgenic thymocytes, we identified several layers of regulation of the innate-like NKT effector program: first, PLZF bound and regulated genes encoding cytokine receptors as well as homing and adhesion receptors; second, PLZF bound and activated T helper-specific transcription factor genes that in turn control T helper specific programs; finally, PLZF bound and suppressed the transcription of Bach2, a potent general repressor of effector differentiation in naive T cells. These findings reveal the architecture of the transcriptional program recruited by PLZF and elucidate how a single transcription factor can drive the developmental acquisition of a broad effector program.
2016-05-24 | GSE81769 | GEO
Project description:Using biotinylation-based ChIP-seq and microarray analysis of both NKT and PLZF-transgenic thymocytes, we identified several layers of regulation of the innate-like NKT effector program. The transcription factor PLZF is induced during the development of innate and innate-like lymphocytes to direct their acquisition of a T helper effector program, but the molecular mechanisms involved are poorly understood. Using biotinylation-based ChIP-seq and microarray analysis of both NKT and PLZF-transgenic thymocytes, we identified several layers of regulation of the innate-like NKT effector program: first, PLZF bound and regulated genes encoding cytokine receptors as well as homing and adhesion receptors; second, PLZF bound and activated T helper-specific transcription factor genes that in turn control T helper specific programs; finally, PLZF bound and suppressed the transcription of Bach2, a potent general repressor of effector differentiation in naive T cells. These findings reveal the architecture of the transcriptional program recruited by PLZF and elucidate how a single transcription factor can drive the developmental acquisition of a broad effector program.
2016-05-24 | GSE81768 | GEO
Project description:LncRNAs played a crucial role in the cell growth, development and some diseases relating to central nerve system.This study suggest that with regulating the LncRNAs expression level we might design novel therapy for spinalcord injury. In this dataset, we profiled the expression pattern of LncRNAs by microarray method after spinal cord injury (SCI). Through Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis seek LncRNAs potential function in the repair of spinal cord injury. Fifteen samples were analyzed. In these sample, we divided into five groups (sham operation, 1 day post-injured, 3 days post-injured, 1 week post-injued and 3 weeks post-injured) and each group contained three mice.After RNA extraction,RNA form mice in the same group were mixed by equal mass for the preparation of microarray.Compared with spinal cord without injury, the differential expression level of LncRNAs had a few changes at 1day post-injury, reached the peak at 1 week after SCI, and subsequently declined until 3 weeks post-injury. Genes with an FDR≤0.05 and a fold-change ≥2 were selected. Subsequently we analysis the significant differential expression genes.
2015-09-01 | E-GEOD-67515 | biostudies-arrayexpress
Project description:To identify genes that PLZF is sufficient to modulate in T cells, we compared CD4+ CD8- (CD4SP) thymocytes that overexpressed PLZF to their wildtype counterparts The transcription factor PLZF is induced during the development of innate and innate-like lymphocytes to direct their acquisition of a T helper effector program, but the molecular mechanisms involved are poorly understood. Using biotinylation-based ChIP-seq and microarray analysis of both NKT and PLZF-transgenic thymocytes, we identified several layers of regulation of the innate-like NKT effector program: first, PLZF bound and regulated genes encoding cytokine receptors as well as homing and adhesion receptors; second, PLZF bound and activated T helper-specific transcription factor genes that in turn control T helper specific programs; finally, PLZF bound and suppressed the transcription of Bach2, a potent general repressor of effector differentiation in naive T cells. These findings reveal the architecture of the transcriptional program recruited by PLZF and elucidate how a single transcription factor can drive the developmental acquisition of a broad effector program.
2016-05-24 | GSE81770 | GEO
Project description:Mephedrone (Meph) is a novel psychostimulant whose recreational consumption is often associated to other drugs, especially alcohol (EtOH). This kind of drug consumption during adolescence is a matter of concern. We studied, in adolescent CD-1 mice, whether low-moderate doses of EtOH could enhance the psychostimulant (locomotor acivity) and reinforcing (conditioned place preference, CPP) effects of mephedrone. Simultaneously we also determined the most relevant transcriptional changes associated to a reinforcing treatment. A single dose of Meph (10 mg/kg, sc) induced an increase of about 100% in locomotor activity, which was a further enhanced by 40% when associated with a dose of EtOH (1 g/kg). The hyperlocomotion was partially antagonized by ketanserin and haloperidol, but only haloperidol blocked the potentiation induced by EtOH. Furthermore, Meph (25 mg/kg) induced significant positive conditioning, which increased by 70% when administered with 0.75 mg/kg EtOH. Microarray analysis of mRNA extracted from anterior striata of the mice used in CPP experiments reported significant modifications in genes related with neurotransmission and synaptic plasticity, which were further validated by Real-time PCR for all three drug-treated groups. Four groups were compared in the study: adolescent Swiss CD-1 mice treated with saline, ethanol, mephedrone or mephedrone + ethanol during the conditioned place preference (CPP) ten-day procedure, aimed at evaluating reward. Twelve samples are provided, which correspond to triplicates of each treatment group. The samples provided were subsequently normalized and analyzed using the GeneSpring GX 7.3.1 software.
2016-08-01 | E-GEOD-58279 | biostudies-arrayexpress
Project description:Pharmacological activation of the transcription factor PPAR gamma lowers blood pressure and improves glucose tolerance in humans. In contrast, naturally occurring mutations (e.g., P467L, V290M) in the ligand binding domain of PPAR gamma in humans leads to severe insulin resistance and early-onset hypertension. Experimental evidence, including whole genome expression profiling, suggests that these mutant versions of PPAR gamma act in a dominant negative manner. Because PPAR gamma is expressed in a variety of cell types and tissues, we generated a transgenic mouse model (SP467L) specifically targeting dominant negative PPAR gamma to the vascular smooth muscle cells in order to determine the action of PPAR gamma in the blood vessel independent of its systemic metabolic actions. In the data set provided herein, we examined the gene expression profile in mesenteric vessels from SP467L mice and their control littermates using the Affymetrix mouse exon 1.0 ST array. We generated transgenic mice specifically targeting expression of mutant dominant negative human PPAR gamma (P467L) to vascular smooth muscle using a smooth muscle-specific promoter (smooth muscle myosin heavy chain or SMMHC). Mesenteric arteries were isolated from 3 male transgenic mice and 4 non-transgenic littermate controls. Total RNA was prepared using conventional methods and quality was assessed using the Bioanalyzer 2100 (Agilent Technologies). For the microarray hybridizations, each sample corresponded to mesenteric artery derived from one mouse. All procedures were conducted at the University of Iowa DNA Core facility using standard Affymetrix protocols. In brief, approximately 50 ng of total RNA was used as input to a two-step amplification procedure (NuGen, http://www.nugeninc.com/) to generate biotin-labeled RNA fragments for hybridization to the Affymetrix mouse exon 1.0 ST array.
2012-09-24 | E-GEOD-36482 | biostudies-arrayexpress