Early Notch signaling programs effector CD8+ T cell differentiation [RNA-Seq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1222845 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR32320400.fastq.gz | Fastqsanger.gz | |||
| SRR32320401.fastq.gz | Fastqsanger.gz | |||
| SRR32320402.fastq.gz | Fastqsanger.gz | |||
| SRR32320403.fastq.gz | Fastqsanger.gz | |||
| SRR32320404.fastq.gz | Fastqsanger.gz |
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Project description:Early Notch signaling programs effector CD8+ T cell differentiation [ATAC-Seq]
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Project description:A better understanding of the mechanisms regulating CD8+ T cell differentiation is essential to develop new strategies to fight infections and cancer. Using genetic mouse models and blocking antibodies, we uncovered cellular and molecular mechanisms by which Notch signaling favors efficient generation of effector CD8+ T cells. Using transcriptional and epigenetic studies, we identified a unique Notch-driven T cell-specific signature. Early Notch signals were associated with chromatin opening in regions occupied by bZIP transcription factors, specifically BATF, known to be important for CD8+ T cell differentiation. Overall, we show that the delivery of early Notch signals controls the molecular and functional fate of CD8+ T cells after infection.
2025-02-21 | GSE289394 | GEO
Project description:A better understanding of the mechanisms regulating CD8+ T cell differentiation is essential to develop new strategies to fight infections and cancer. Using genetic mouse models and blocking antibodies, we uncovered cellular and molecular mechanisms by which Notch signaling favors efficient generation of effector CD8+ T cells. Using transcriptional and epigenetic studies, we identified a unique Notch-driven T cell-specific signature. Early Notch signals were associated with chromatin opening in regions occupied by bZIP transcription factors, specifically BATF, known to be important for CD8+ T cell differentiation. Overall, we show that the delivery of early Notch signals controls the molecular and functional fate of CD8+ T cells after infection.
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Project description:Phosphatidylinositol-3-kinase p110 delta (PI3Kp110δ) is pivotal for CD8+ T cell immune responses. To inform how PI3Kp110δ regulates CD8+ T cells, the current study focuses on PI3Kp110δ controlled transcriptional programs and reveals how PI3Kp110δ selectively induces and represses expression of key genes that create a cytotoxic T cell (CTL). The data identify differences in PI3Kp110δ regulated transcriptional programs between naïve and cytotoxic T cells including differential control of cytolytic effector molecules, costimulatory receptors and the critical inhibitory receptors CTLA4 and SLAMF6. However, common to both naïve and effector cells is PI3Kp110δ control of the production of chemokines and cytokines that orchestrate communication between the adaptive and innate immune system. The study provides a comprehensive resource for understanding how PI3Kp110δ uses multiple mechanisms dependent on Protein Kinase B/AKT, FOXO1 dependent and independent mechanisms and mitogen-activated protein kinases (MAPK) to direct CD8+ T cell fate.
2021-06-14 | PXD025046 | Pride
Project description:Phosphatidylinositol-3-kinase p110 delta (PI3Kp110δ) is pivotal for CD8+ T cell immune responses. To inform how PI3Kp110δ regulates CD8+ T cells, the current study focuses on PI3Kp110δ controlled transcriptional programs and reveals how PI3Kp110δ selectively induces and represses expression of key genes that create a cytotoxic T cell (CTL). The data identify differences in PI3Kp110δ regulated transcriptional programs between naïve and cytotoxic T cells including differential control of cytolytic effector molecules, costimulatory receptors and the critical inhibitory receptors CTLA4 and SLAMF6. However, common to both naïve and effector cells is PI3Kp110δ control of the production of chemokines and cytokines that orchestrate communication between the adaptive and innate immune system. The study provides a comprehensive resource for understanding how PI3Kp110δ uses multiple mechanisms dependent on Protein Kinase B/AKT, FOXO1 dependent and independent mechanisms and mitogen-activated protein kinases (MAPK) to direct CD8+ T cell fate.
2021-06-14 | PXD025061 | Pride
Project description:Memory CD8+ T cells are an essential component of protective immunity. Signaling via mechanistic target of rapamycin (mTOR) has been implicated in the regulation of the differentiation of effector and memory T cells. However, little is understood about the mechanisms that control mTOR activity, or the effector pathways regulated by mTOR, in this process. We describe here that tuberous sclerosis 1 (Tsc1), a regulator of mTOR signaling, plays a crucial role in promoting the differentiation and function of memory CD8+ T cells in response to Listeria monocytogenes infection. Mice with specific deletion of Tsc1 in antigen-experienced CD8+ T cells evoked normal effector responses, but were markedly impaired in the generation of memory T cells and their recall responses to antigen re-exposure in a cell-intrinsic manner. Tsc1 deficiency suppressed the generation of memory-precursor effector cells (MPECs) while promoting short-lived effector cell (SLEC) differentiation. Functional genomic analysis indicated that Tsc1 coordinated gene expression programs underlying immune function, transcriptional regulation and cell metabolism. Furthermore, Tsc1 deletion led to excessive mTORC1 activity and dysregulated cellular metabolism including glycolytic and oxidative metabolism. These findings establish a Tsc1-mediated checkpoint in linking immune signaling and cell metabolism to orchestrate memory CD8+ T cell development and function. We used microarrays to explore the gene expression profiles differentially expressed in OVA-specific CD8+ T-cells from wild-type (WT; Tsc1-fl/fl and cre-negative) and Tsc1-/- (Tsc1-fl/fl and Granzyme B-cre-positive) mice
2014-09-20 | E-GEOD-61591 | biostudies-arrayexpress
Project description:Here we implemented a simple dendritic cell (DC)-mediated immunization approach to study the effects of commonly used adjuvants, Toll like receptor (TLR) ligands, on effector CD8 T cell differentiation and memory T cell development. To our surprise, we found that the TLR4 ligand LPS was far more superior to other TLR ligands in generating memory CD8 T cells upon immunization. LPS boosted clonal expansion similar to the other adjuvants, but fewer of the activated CD8 T cells died during contraction, generating a larger pool of memory cells. Intriguingly, monophosphoryl lipid A (MPLA), another TLR4 ligand, enhanced clonal expansion of effector CD8 T cells, but also promoted their terminal differentiation and contraction; thus, fewer memory CD8 T cells formed and MPLA-primed animals were less protected against secondary infection compared to those primed with LPS. Furthermore, gene expression profiling revealed that LPS-primed effector cells displayed a stronger pro-memory gene expression signature, whereas the gene expression profile of MPLA-primed effector cells had aligned closer with terminal effector CD8 T cells. Mice that contain small number of P14 CD8 T cells were immunized with DC-33 either alone or in combination with LPS or MPLA. KLRG1loIL-7Rhi MPECs were purified by FACS sort, and mRNA isolated from MPECs was subjected to whole-genome expression profiling using Illumina MouseWG-6 v2.0 Expression BeadChip.
2014-06-03 | E-GEOD-50764 | biostudies-arrayexpress
Project description:DNMT3a is a de novo DNA methyltransferase expressed robustly after T cell activation that regulates plasticity of CD4+ T cell cytokine expression. Here we show that DNMT3a is critical for directing early CD8+ T cell effector and memory fate decisions. While effector function of DNMT3a knockout T cells is normal, they develop more memory precursor and fewer terminal effector cells in a T cell intrinsic manner compared to wild-type animals. Rather than increasing plasticity of differentiated effector CD8+ T cells, loss of DNMT3a biases differentiation of early effector cells into memory precursor cells. This is attributed in part to ineffective repression of Tcf1 expression in knockout T cells, as DNMT3a localizes to the Tcf7 promoter and catalyzes its de novo methylation in early effector WT CD8+ T cells. This data identifies DNMT3a as a crucial regulator of CD8+ early effector cell differentiation and effector versus memory fate decisions. Examination of global genomic DNA methylation by MBD-seq in naïve CD8 T cells and CD8 T cells 8 days post Vaccinia-Ova infection, comparing OT1 TCR-Tg CD8 T cells isolated from WT and T cell conditional DNMT3a KO mice.
2016-08-20 | E-GEOD-85823 | biostudies-arrayexpress
Project description:IL-2 and IL-21 are closely related cytokines that might have arisen by gene duplication. Both cytokines promote the function of effector CD8+ T cells, but their distinct effects on antigen-driven differentiation of naïve CD8+ T cells into effector CD8+ T cells are not clearly understood. We found that antigen-induced expression of eomesodermin and maturation of naïve CD8+ T cells into granzyme B and CD44 expressing effector CD8+ T cells was enhanced by IL-2, but, unexpectedly, suppressed by IL-21. Furthermore, IL-21 repressed expression of IL-2Ra and inhibited IL-2-mediated acquisition of a cytolytic CD8+ T cell phenotype. Despite its inhibitory effects, IL-21 did not induce anergy, but instead potently enhanced the capacity of cells to mediate tumor regression upon adoptive transfer. In contrast, IL-2, surprisingly, impaired the subsequent anti-tumor function of transferred cells. Gene expression studies revealed a distinct IL-21-program that was characterized phenotypically by increased expression of L-selectin and functionally by enhanced anti-tumor immunity that was not reversed by secondary in vitro stimulation with antigen and IL-2. Thus, the efficacy of CD8+ T cells for adoptive immunotherapy can be influenced by opposing differentiation programs conferred by IL-2 and IL-21, a finding with important implications for the development of cellular cancer therapies. Two-condition experiment: Cytokine-exposed t-cells subsequentially restimulated without cytokine vs. control t-cells without cytokine subsquentially restimulated without cytokine. 3 independent experiments - 1 with experimental RNA labeled with Cy5, control with Cy3, and 2 with dyes-swapped Keywords: Cytokine exposure comparison Comparitive analysis of cytokine effects on lymphocyte gene expression. GSM265712.gpr (S89_1_IL2_0.gpr): Cy3 - control, Cy5 - experimental GSM265713.gpr (S90_1_IL15_0.gpr): Cy3 - control, Cy5 - experimental GSM265714.gpr (S91_1_IL21_0.gpr): Cy3 - control, Cy5 - experimental GSM265715.gpr (S27_2_0_IL2.gpr): Cy3 - experimental, Cy5 - control GSM265716.gpr (S29_2_0_IL15.gpr): Cy3 - experimental, Cy5 - control GSM265717.gpr (S30_2_0_IL21.gpr): Cy3 - experimental, Cy5 - control GSM265718.gpr (S31_3_0_IL2.gpr): Cy3 - experimental, Cy5 - control GSM265719.gpr (S33_3_0_IL15.gpr): Cy3 - experimental, Cy5 - control
2010-05-26 | E-GEOD-10403 | biostudies-arrayexpress
Project description:Antigen-specific effector CD8+ T cells deficient in Blimp-1 (Prdm1) do not acquire maximal effector functions, evade terminal differentiation, and more rapidly acquire some hallmark properties of memory CD8+ T cells. In this study, we compared the gene expression profiles of wildtype and Prdm1-/- LCMV-specific effector CD8+ T cells to better understand the molecular mechanisms underlying this striking phenotype. DNA microarray analysis was performed of DbGP33-41 and DbNP396-404 tetramer-positive effector CD8+ T cells FACS-sorted at day 8 post-LCMV infection from four independent samples of either Blimp-1 conditional knockout mice (CKO; Blimp-1flox/flox x GranzymeB-cre+) or wildtype (WT) littermate controls.
2010-08-19 | E-GEOD-17211 | biostudies-arrayexpress