Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA179131 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR611652.fastq.gz | Fastqsanger.gz | |||
| SRR611653.fastq.gz | Fastqsanger.gz | |||
| SRR611654.fastq.gz | Fastqsanger.gz | |||
| SRR611655.fastq.gz | Fastqsanger.gz | |||
| SRR611656.fastq.gz | Fastqsanger.gz |
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Project description:gd T cells are major innate sources of interleukin-17 (IL-17) and interferon-g (IFN-g), which are differentially produced by two thymically-derived subsets segregated on CD27 expression. However, the molecular mechanisms that program the functional differentiation of gd cells remain incompletely understood. Here we show that CD27+ gd cells are epigenetically committed to express Ifng but not Il17, whereas CD27- gd cells spontaneously make IL-17 but can be induced to produce IFN-g under specific inflammatory conditions. This “plastic” behavior of CD27- gd cells associates with permissive histone H3 marks at loci encoding Ifng and upstream “type 1” transcription factors. By contrast, Il17 and related “type 17” factors are epigenetically and transcriptionally active in CD27- but silenced in CD27+ gd cells. Hence, stable versus plastic behaviors of gd cell subsets are controlled by integrated epigenetic and transcriptional mechanisms that regulate the expression of “master” transcription factors and effector cytokine genes.
2013-09-01 | GSE42098 | GEO
Project description:gd T cells are major innate sources of interleukin-17 (IL-17) and interferon-g (IFN-g), which are differentially produced by two thymically-derived subsets segregated on CD27 expression. However, the molecular mechanisms that program the functional differentiation of gd cells remain incompletely understood. Here we show that CD27+ gd cells are epigenetically committed to express Ifng but not Il17, whereas CD27- gd cells spontaneously make IL-17 but can be induced to produce IFN-g under specific inflammatory conditions. This M-bM-^@M-^\plasticM-bM-^@M-^] behavior of CD27- gd cells associates with permissive histone H3 marks at loci encoding Ifng and upstream M-bM-^@M-^\type 1M-bM-^@M-^] transcription factors. By contrast, Il17 and related M-bM-^@M-^\type 17M-bM-^@M-^] factors are epigenetically and transcriptionally active in CD27- but silenced in CD27+ gd cells. Hence, stable versus plastic behaviors of gd cell subsets are controlled by integrated epigenetic and transcriptional mechanisms that regulate the expression of M-bM-^@M-^\masterM-bM-^@M-^] transcription factors and effector cytokine genes. ChIP was carried out on FACS-sorted cells from pooled spleen/ lymph nodes. The following antibodies were used: anti-histone H3K4me2 (07-030, Millipore) and anti-histone H3k27me3 (07-449, Millipore). Between 105 - 106 cells were crosslinked with formaldehyde and nuclei were isolated and sonicated with a Sanyo Soniprep 150 at an amplitude of 10 microns with 17 times 10s bursts, resulting in 200M-bM-^@M-^S400bp chromatin fragments. IP was carried out as previously described 49. The Immunoprecipitated DNA released from crosslinked proteins was extracted with the QiaQuick kit (Qiagen) in accordance with the manufacturerM-BM-4s instructions. Deep sequencing was performed at the GeneCore facility of EMBL (http://www.genecore.embl.de/). At least 1 ng of immunoprecipitated DNA was used for library preparation according to the Illumina protocol.
2013-09-01 | E-GEOD-42098 | biostudies-arrayexpress
Project description:Multipotential naïve CD4+ T cells differentiate into distinct lineages including T helper 1 (Th1), Th2, Th17, and inducible T regulatory (iTreg) cells. The remarkable diversity of CD4+ T cells begs the question whether the observed changes reflect terminal differentiation with heritable epigenetic modifications or plasticity in T cell responses. We generated genome-wide histone H3 lysine 4 (H3K4) and lysine 27 (H3K27) trimethylation maps in naïve, Th1, Th2, Th17, iTreg, and natural (n)Treg cells. We found that although modifications of signature cytokine genes (Ifng, Il4, and Il17) partially conform to the expectation of lineage commitment, critical transcription factors such as Tbx21 exhibit a broad spectrum of epigenetic states, consistent with our demonstration of T-bet and IFN-? induction in nTreg cells. Our data suggest an epigenetic mechanism underlying the specificity and plasticity of effector and regulatory T cells and also provide a framework for understanding complexity of CD4+ T helper cell differentiation. Experiment Overall Design: Different T helper subsets are profiled for mRNA expression.
2009-01-16 | E-GEOD-14308 | biostudies-arrayexpress
Project description:Epigenetic Mechanisms Underlie T Cell Plasticity
| PRJNA111305 | ENA
Project description:gd T cells are increasingly understood to play critical roles in host defense and can also contribute to immune mediated pathology; however, their origins remain poorly understood. There is growing evidence suggesting that immature bipotent progenitors in the thymus are instructed to adopt the ab and γδ fates, respectively, by differences in T cell receptor (TCR) signal strength or duration, with stronger and more prolonged signals directing adoption of the gd fate. These differences in TCR signaling instruct fate through graded induction of Id3, which in turn, produces graded reductions in the ability of E box DNA binding proteins (E proteins) to bind DNA. While E proteins play a central role in regulating lymphoid fate decisions, their downstream gene targets through which they specify fate have not been identified. Understanding how E proteins control gd lineage commitment requires a comprehensive, network-based approach. Consequently, we employed ChIP-Seq to identify the enhancers whose occupancy by E-proteins was altered by TCR signaling during gd lineage commitment and we identified their targets using a chromosome capture method termed Hi-C. These data were then integrated into a comprehensive, E-protein-focused, genome-wide network describing the genomic reorganization that occurs during gd lineage commitment. These studies revealed that E protein occupancy of enhancers was far more dramatically remodeled in progenitors adopting the gd lineage fate than in uncommitted progenitors exposed to the same selecting environment and has led to the identification of specific regulatory elements through which gd lineage commitment and effector function is controlled. One such element plays a critical role in controlling the expression of the transcription factor (TF) ThPOK, as well as the effector function of γδ T cells. Thus, our comprehensive approach has provided critical new insights into the molecular processes orchestrating gd lineage commitment and provides a framework for molecular dissection of both lineage commitment and effector function.
2021-03-10 | GSE162290 | GEO
Project description:gd T cells are increasingly understood to play critical roles in host defense and can also contribute to immune mediated pathology; however, their origins remain poorly understood. There is growing evidence suggesting that immature bipotent progenitors in the thymus are instructed to adopt the ab and γδ fates, respectively, by differences in T cell receptor (TCR) signal strength or duration, with stronger and more prolonged signals directing adoption of the gd fate. These differences in TCR signaling instruct fate through graded induction of Id3, which in turn, produces graded reductions in the ability of E box DNA binding proteins (E proteins) to bind DNA. While E proteins play a central role in regulating lymphoid fate decisions, their downstream gene targets through which they specify fate have not been identified. Understanding how E proteins control gd lineage commitment requires a comprehensive, network-based approach. Consequently, we employed ChIP-Seq to identify the enhancers whose occupancy by E-proteins was altered by TCR signaling during gd lineage commitment and we identified their targets using a chromosome capture method termed Hi-C. These data were then integrated into a comprehensive, E-protein-focused, genome-wide network describing the genomic reorganization that occurs during gd lineage commitment. These studies revealed that E protein occupancy of enhancers was far more dramatically remodeled in progenitors adopting the gd lineage fate than in uncommitted progenitors exposed to the same selecting environment and has led to the identification of specific regulatory elements through which gd lineage commitment and effector function is controlled. One such element plays a critical role in controlling the expression of the transcription factor (TF) ThPOK, as well as the effector function of γδ T cells. Thus, our comprehensive approach has provided critical new insights into the molecular processes orchestrating gd lineage commitment and provides a framework for molecular dissection of both lineage commitment and effector function.
2021-03-10 | GSE162291 | GEO
Project description:Homeostatic plasticity, a form of synaptic plasticity, maintains the fine balance between overall excitation and inhibition in developing and mature neuronal networks. Although the synaptic mechanisms of homeostatic plasticity are well characterized, the associated transcriptional program remains poorly understood. We show that the Kleefstra syndrome-associated protein, EHMT1, plays a critical and cell-autonomous role in synaptic scaling by responding to attenuated neuronal firing or sensory drive. Chronic activity deprivation increased the amount of neuronal dimethylated H3 at lysine 9 (H3K9me2), the catalytic product of EHMT1 and an epigenetic marker for gene repression. Genetic knockdown and pharmacological blockade of EHMT1 or EHMT2 prevented the increase of H3K9me2 and synaptic scaling up. Furthermore, BDNF repression was preceded by EHMT1/2-mediated H3K9me2 deposition at the Bdnf promoter during synaptic scaling up, both in vivo or in vivo. These findings suggest that changes in chromatin state through H3K9me2 governs a repressive program to achieve synaptic scaling. 12 samples (4 conditions in biological triplicate), 3 wt, 3 wt tetradotoxin treated, 3 k.d., 3 k.d. tetradotoxin treated
2016-06-30 | E-GEOD-68960 | biostudies-arrayexpress
Project description:The two major human gd T cell subsets, Vd1 and Vd2, display differences in tissue tropism and agonist responses, but we have little insight into global differences that may exist at the gene expression level. This is due to the small numbers of these cells that can be obtained from healthy donors, which limit comprehensive, comparative gene expression analyses. We established a culture method that expands Vd1 and Vd2 cells from the same PBL preparation to levels sufficient for sorting and microarray analysis. Although the subsets were expanded identically (anti-TCR mAb, plus IL-15), 392 and 614 genes were identified, which were differentially expressed in the two subsets, from two donors, respectively. Approximately 4,500 genes changed in both subsets following PMA/ionomycin treatment; about 50% of these genes were subset-specific. Both subsets responded to a crude LPS preparation, but only 6% of the responsive genes were the same. The differentially expressed genes were consistent with Vd2 cells being more inflammatory and Vd1 cells having more of a regulatory phenotype. Both subsets expressed transcripts encoding an array of innate and NK cell receptors, supporting the relationship of gd?T cells to the innate immune system. Our results show that circulating Vd1 and Vd2 subsets in humans have considerable, inherent differences in gene expression following treatment with non-TCR agonists, supporting unique functional roles for these cells in vivo.
2007-11-08 | E-GEOD-3720 | biostudies-arrayexpress
Project description:Knowing the gene expression profiles of drug-metabolizing enzymes and transporters throughout gestation is important for understanding the mechanisms of pregnancy-induced changes in drug pharmacokinetics. In this study, we compared gene expression of drug-metabolizing enzymes and transporters in the maternal liver, kidney, small intestine, and placenta of pregnant mice throughout gestation by microarray analysis. Specifically, we investigated cytochrome P450 (Cyp), UDP-glucuronosyltranserase (Ugt), and sulfotransferase (Sult), as well as ATP-binding cassette (Abc) and solute carrier (Slc) transporters. We found that relatively few Ugt and Sult genes were impacted by pregnancy in maternal tissues and placenta. Cyp1a2, most Cyp2 isoforms, Cyp3a11, and Cyp3a13 in the liver were down-regulated, with the greatest changes occurring on gestation days (gd) 15 and 19 compared to non-pregnant controls (gd 0). However, Cyp2d40, Cyp3a16, Cyp3a41a, Cyp3a41b, and Cyp3a44 in the liver were induced throughout pregnancy. Cyp expression in mid-gestation placenta (gd 10 and 15) was generally greater than that in term placenta (gd 19). There were also notable changes in Abc and Slc transporters. Abcc3 in the liver was down-regulated by 60%, and Abcb1a, Abcc4, and Slco4c1 in the kidney were down-regulated by 30-60% on gd 15 and 19 versus gd 0. Abcc5 in the placenta was induced 3-fold on gd 10 versus gd 15 and 19, whereas Slc22a3 expression in the placenta on gd 10 was 90% lower than that on gd 15 and 19. Overall, this study demonstrates important gestational age-dependent expression of drug-metabolizing enzymes and transporter genes, which may have mechanistic relevance to human pregnancy. Ninety pregnant mice at gestational days 0, 7.5, 10, 15, and 19 (n = 5-6 per gestational age) were used for the maternal liver, kidney, small intestine and placenta. The placentas were collected on gestational days 10, 15, and 19.
2013-10-08 | E-GEOD-41438 | biostudies-arrayexpress
Project description:Single cell RNA-seq study of T lymphocyte differentiation WT and LAT deficient mice in order to deciphy gd T-cell lineage commitment.
2022-01-01 | GSE184544 | GEO