Eomes broadens the scope of CD8 T cell memory by inhibiting apoptosis in low-affinity cells
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ABSTRACT:
PROVIDER: PRJNA484766 | ENA |
REPOSITORIES: ENA
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Project description:The memory CD8 T cell pool must select for high-affinity clones to efficiently counter re-infection yet must retain a level of clonal diversity to allow recognition of pathogens with mutated immuno-dominant epitopes. How this is mediated is unclear, especially in the context of a selective drive for antigen-affinity. We find that low-affinity memory exclusively depends on the transcription factor Eomes in the first days after antigen encounter. Eomes is induced at low activating signal strength and directly drives transcription of the pro-survival protein Bcl-2. At higher signal intensity T-bet is induced which suppresses Bcl-2, generating a survival advantage for low-affinity cells. High-affinity cells form memory independent of Eomes and have a proliferative advantage over low-affinity cells, which compensates for their survival deficit. Thus, we demonstrate on a molecular level how sufficient diversity of the memory pool is established in an environment of affinity-based selection.
2020-08-01 | GSE118174 | GEO
Project description: Not available
| S-EPMC7077837 | biostudies-literature
Project description:Eomesodermin (Eomes) is a transcription factor with a crucial role regulating cytotoxic function, development and survival of immune cells. Although it is known that γδ T cells can express Eomes, its function on those cells is still largely unknown. Using Eomes-IRES-GFP mice we were able to sort for Eomes+ and Eomes‒ γδ T cells populations and get their gene expression profiles, bringing light to the role of Eomes on γδ T cells.
2017-04-10 | GSE85585 | GEO
Project description:High amount of Eomes might drive T cell exhaustion. In order to understand how Eomes contributes to exhaustion of CD8+ T cell in the TME as a transcription factor, we conducted anti-Eomes ChIPseq analysis of control OT-I cells and Eomes-overexpressing OT-I cells.
2018-11-26 | GSE122888 | GEO
Project description:Memory CD8+ T cells have the ability to provide lifelong immunity against pathogens. Although memory features generally arise after challenge with a foreign antigen, naïve CD8 single positive (SP) thymocytes may acquire phenotypic and functional characteristics of memory cells in response to cytokines such as interleukin-4. This process is associated with the induction of the T-box transcription factor Eomesodermin (EOMES). However, the underlying molecular mechanisms remain ill-defined. Using epigenomic profiling, we show that these innate memory CD8SP cells acquire only a portion of the active enhancer repertoire of conventional memory cells. This reprograming is secondary to EOMES recruitment, mostly to RUNX3-bound enhancers. Furthermore, EOMES is found within chromatin-associated complexes containing BRG1 and promotes the recruitment of this chromatin remodelling factor. Also, the in vivo acquisition of EOMES-dependent program is BRG1-dependent. In conclusion, our results support a strong epigenetic basis for the EOMES-driven establishment of CD8+ T cell innate memory program.
2019-06-06 | PXD014142 | Pride
Project description:T-bet and Eomes are related T-box transcription factors that control NK cell development. This study was designed to understand the specific roles of Eomes and T-bet in regulating gene expression. RNAseq data were generated for immature (CD11b- CD27+) and mature (CD11b+ CD27-) NK cells from T-bet KO (Tbet Ho) or control mice (Tbet WT) or from Eomes KO (Eomes Ho) or control mice (NK-Cre). Three samples were generated for each condition (Tri 1, 2, 3).
2021-05-10 | GSE168240 | GEO
Project description:To gain mechanistic insights into how EOMES regulates CD4+ T-cell differentiation and function, we performed an RNA-seq analysis using Eomes-GFP reporter mice (Eomes+/GFP) to isolate GFP+ (EOMES+) and GFP- (EOMES-) CD4+ T-cells by FACS sorting. We also sequenced RNA from Eomes-deficient GFP+ and GFP- CD4+ T-cells isolated from EomesΔT/GFP knock-out mice, in which one Eomes allele is disrupted by GFP insertion and the DNA-binding domain of the other allele is deleted in T cells by Lck-driven Cre recombinase. Hence, we had two populations of GFP+ cells where the EOMES locus was transcribed, one with a transcriptionally active EOMES protein (Eomes+/GFP) and another one with no transcriptionally active EOMES (EomesΔT/GFP), plus the respective GFP-negative controls isolated from the same mice. A homogeneous population of EOMES-expressing CD4+ T cells were obtained by transferring naïve sorted CD25- CD45RBhigh CD4+ T-cells isolated from Eomes+/GFP reporter or EomesΔT/GFP knock-out donor animals into Rag2-/- mice. After three weeks of adoptive transfer GFP+ and GFP- CD4+ T-cell populations from these mice were FACS-sorted for transcriptome analysis by RNA sequencing.
2020-10-01 | GSE145145 | GEO
Project description:Skin samples were analyzed through Seq-Scope.
2022-07-22 | GSE186601 | GEO
Project description:The cortical area map is initially patterned by transcription factor (TF) gradients in the neocortical primordium, which define a protomap in the embryonic ventricular zone (VZ). However, mechanisms that propagate regional identity from VZ progenitors to cortical plate (CP) neurons are unknown. Here we show that the VZ, subventricular zone (SVZ), and CP contain distinct molecular maps of regional identity, reflecting different gene expression gradients in radial glia progenitors, intermediate progenitors, and projection neurons, respectively. The intermediate map in SVZ is modulated by Eomes (also known as Tbr2), a T-box TF. Eomes inactivation caused rostrocaudal shifts in SVZ and CP gene expression, with loss of corticospinal axons and gain of corticotectal projections. These findings suggest that cortical areas and connections are shaped by sequential maps of regional identity, propagated by the Pax6 ? Eomes ? Tbr1 TF cascade. In humans, PAX6, EOMES, and TBR1 have been linked to intellectual disability and autism. To determine the role of Eomes in the propagation of the protomap to cortical plate neurons, used microarray analysis of E14.5 cortex from five wild type and three Eomes knockout mice.
2013-04-02 | E-GEOD-43387 | biostudies-arrayexpress