Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA338284 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Cellular binary fate decisions require the progeny to silence genes associated with the alternative fate. The major subsets of alpha:beta T cells have been extensively studied as a model system for fate decisions. While the transcription factor RUNX3 is required for the initiation of Cd4 silencing in CD8 T cell progenitors, it is not required to maintain the silencing of Cd4 and other helper T lineage genes. The other runt domain containing protein, RUNX1, silences Cd4 in an earlier T cell progenitor, but this silencing is reversed whereas the gene silencing after RUNX3 expression is not reverse. Therefore, we hypothesized that RUNX3 and not RUNX1 recruits other factors that maintains the silencing of helper T lineage genes in CD8 T cells. To this end, we performed a proteomics screen of RUNX1 and RUNX3 to determine candidate silencing factors.
2019-11-12 | PXD007511 | Pride
Project description:Chronic viral infections are characterized by a state of CD8 T cell dysfunction termed exhaustion. A better understanding of the mechanisms that regulate CD8 T cell responses during chronic infection is required to improve immunotherapies that restore function in exhausted CD8 T cells. Here we identify a novel population of virus-specific CD8 T cells with a T follicular helper (Tfh)-like signature in mice chronically infected with lymphocytic choriomeningitis virus (LCMV). These Tfh-like CD8 T cells expressed the programmed cell death-1 (PD-1) inhibitory receptor but at the same time also expressed co-stimulatory molecules and had a gene signature that was related to CD8 T cell memory precursor cells and hematopoietic stem cells (HSC). These Tfh-like CD8 T cells acted as stem cells during chronic infection undergoing self-renewal and also differentiating into the terminally exhausted CD8 T cells that were present in both lymphoid and non-lymphoid tissues. The Tfh-like CD8 T cells were found only in lymphoid tissues and resided predominantly in the T cell zones along with naïve CD8 T cells. Interestingly, the proliferative burst after PD-1 blockade came almost exclusively from this Tfh-like CD8 T cell subset. Importantly, the transcription factor TCF1 played a cell intrinsic and essential role in the generation of Tfh-like CD8 T cells. Taken together, our study identifies Tfh-like CD8 T cells as the critical subset for maintaining the pool of virus-specific CD8 T cells during chronic infection and as the cells that proliferate after PD-1 blockade. These findings provide a better understanding of T cell exhaustion and have implications towards optimizing PD-1 directed immunotherapy. 8 samples isolated from CD8 T-cells in LCMV clone 13 GK1.5 infected mice (2 naïve, 3 CXCR5+Tim3-, 3 CXCR5-Tim3+) cells were analyzed
2016-08-02 | E-GEOD-84105 | biostudies-arrayexpress
Project description:We have discovered a small subpopulation of virus-specific CD8 T-cells that sustains the T-cell response in chronic infections. These cells are defined by - and depend on - the expression of the transcription factor Tcf1 (T cell factor 1) and show key characteristics of central memory cells while lacking an effector signature. Unlike conventional memory cells, Tcf1+ T-cells display hallmarks of an âexhaustedâ phenotype, including the expression of certain inhibitory receptors. Naive Tcf1-GFP+ P14 cells (Naive) were transferred into Vb5 recipient mice (CD45.1) prior to infection with LCMV clone 13 (c13). Tcf1-GFP+ P14 cells (chronic Tcf1+) and Tcf1-GFP- P14 cells (chronic Tcf1-) were flow sorted on day 28 post infection. Naive Tcf1-GFP+ P14 cells (Naive) were also transferred into C57BL/6 hosts (CD45.1.2) prior to infection with LCMV Armstrong (Arm). Tcf1-GFP+ P14 cells (memory Tcf1+) and Tcf1-GFP- P14 cells (memory Tcf1-) were flow sorted on day 28 post infection. Total RNA was extracted, cDNA libraries prepared and sequencing was performed using Illumina HiSeq 2500 technology.
2016-08-22 | E-GEOD-83978 | biostudies-arrayexpress
Project description:Translational profiling of in vivo virus-specific CD8 T cells
| PRJNA291699 | ENA
Project description:T-cell exhaustion is frequently observed during chronic viral infection and cancer. How exhausted T cells persist in the presence of immunosuppression is unclear. Here, we showed that virus-specific CD8 T cells differentiate into Tfh-like TCF1highTim3lowBlimp1low progenitors before the chronic phase of viral infection, which persist better than and can give rise to more terminal TCF1lowTim3highBlimp1high cells. Differentiation of TCF1high cells is driven by master regulator TCF1. Cell-intrinsic TCF1 deficiency led to sharp contraction and eventual deletion of virus-specific CD4 and CD8 T cells and uncontrolled viremia
2016-12-22 | GSE85367 | GEO
Project description:We mapped genome-wide Tcf1 binding locations in mature CD8 T cells to identify its direct target genes. This experiment aims to identify genome-wide binding locations for Tcf1 transcription factor in mature CD8 T cells. The CD8 T cells were isolated from wild-type C57BL/6 mice by negative selection. The chromatin fragments were immunoprecipitated by an anti-Tcf1 antiserum or control rabbit serum (without immunization). The immunoprecipitated fragments were then used in high throughput sequencing. Data processing then revealed >3000 high-confidence Tcf1 binding peaks across the CD8 T cell genome. One important finding is that Tcf1 binds directly to Cd4 gene silencer, and thus explain its important role in suppressing the CD4 coreceptor in mature CD8 T cells.
2014-03-05 | E-GEOD-52070 | biostudies-arrayexpress
Project description:Comparison of epigenome and Tcf1 occupancy between control and Tcf1/Lef1-deficient CD8 T cells Control mice or those are deficient for Tcf1 and Lef1 transcription factors (deleted by CD4-Cre) were used to isolate thymocytes. The thymocytes were surface-stained to identify TCRbeta high, CD69â, CD24â CD8+ subsets. These cells were sorted for ChIPseq analysis of various histone marks. Control mice or those are deficient for Tcf1 (deleted by CD4-Cre) were used to isolate thymocytes. The splenocytes were surface-stained to identify TCRbeta high, CD8+ subsets. These cells were sorted for ChIPseq analysis of Tcf1 binding locations.
2016-02-12 | E-GEOD-73239 | biostudies-arrayexpress
Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.
| S-EPMC8784167 | biostudies-literature
Project description:HIV cure efforts are increasingly focused on harnessing CD8 T cell functions; however, a deeper understanding of CD8 T cells promoting HIV control is necessary to properly inform therapeutic approaches. Here, we identified a novel TOX-expressing CD8 T cell population associated with control of SIV infection in lymphoid tissue of rhesus macaques defined as an antigen-responsive TCF1+ CD39+ subset expressing high levels of TOX and inhibitory receptors but lower levels of canonical cytolytic molecules such as granzyme B, granzyme A, and perforin. Transcriptional analysis of SIV-specific CD8 T cells, as well as proteomic analysis of purified CD8 T cell subsets, revealed these TCF1+ CD39+ cells as an intermediate effector population retaining stem-like features while maintaining a lineage relationship with terminal effector cells. TCF1+ CD39+ CD8 T cells expressed higher levels of CXCR5 than terminally differentiated cells, were found at higher frequency in follicular micro-environments, and were preferentially located in the proximity of SIV-RNA+ cells both in lymph node T cell zone and B cell follicles. Importantly, their frequency was strongly associated with reduced plasma viremia and lower reservoir size. Finally, we confirmed the presence of a highly similar TOX-enriched TCF1+ CD39+ cell population in lymph node biopsies from ART-naïve and ART-treated people living with HIV. Collectively, these data identify a unique population of lymphoid CD8 T cells possessing both stem-like and effector properties that contribute to limiting HIV/SIV persistence.
2024-06-11 | PXD050498 | Pride
Project description:Impact of Tcf1 and Lef1 deficiency on histone marks and Tcf1 binding in CD8 T cells
| PRJNA296434 | ENA