D879124d-1e4c-43f8-9497-d56db78c5fc2 - samples
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00001006962 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:The transcriptome of peripheral blood cells (PBMCs) from control or patients with an activation mutation on the STAT1 gene was analyzed.
This analysis aimed to identify the major changes in the circulating immune cells of patients with STAT1 mutation and compare this with the result of the perturbation prediction tool huva (human variation, R).
PBMCs were prepared by density centrifugation and cultured ex vivo for 4 hours in RPMI prior to total RNA extraction.
| EGAS00001005041 | EGA
Project description:The Open Problems Perurbation Prediction (OP3) dataset is to-date the largest single-cell small molecule perturbation dataset in primary tissue with multiple donor replicates. Compounds are dosed in cultured peripheral blood mononuclear cells (PBMCs), enabling the robust computation of perturbation effects on gene expression across four distinct cell type populations: T-cells, B-cells, NK cells, and Myeloid cells. This dataset is the basis for the OP3 benchmark, which evaluates machine learning models on the task of extrapolation perturbation effects into unseen cell types.
2024-10-22 | GSE279945 | GEO
Project description:This study aimed to analyze and compare the test transcripts of peripheral blood mononuclear cells (PBMCs) isolated from 4 healthy donors and 4 septic patients' whole blood.
2024-08-15 | GSE241238 | GEO
Project description:We tested the expression profile of 1146 miRNAs in PBMCs of 19 MS patients and 14 controls (discovery sample) and we explored their function either in vivo by performing a whole-genome mRNA profiling in same patients and in silico using bioinformatic prediction tool (miRbase software). These approaches lead to the identification of putative genetic targets of these miRNAs which could be implicated in the ethiopathogenesis of the disease.
2011-02-27 | E-MTAB-358 | biostudies-arrayexpress
Project description:We tested the expression profile of 1146 miRNAs in PBMCs of 19 MS patients and 14 controls (discovery sample) and we explored their function either in vivo by performing a whole-genome mRNA profiling in same patients and in silico using bioinformatic prediction tool (miRbase software). These approaches lead to the identification of putative genetic targets of these miRNAs which could be implicated in the ethiopathogenesis of the disease.
2011-02-27 | E-MTAB-359 | biostudies-arrayexpress
Project description:We aimed to study the function of NKT, MAIT and V[gamma]9V[delta]2 T-cells in a population of people with cancer. To select appropraite immune parameters to study, we wanted to compare and contrast the expression of immune-related genes in human PBMCs following NKT, MAIT and V[gamma]9V[delta]2 T-cell activation. Aim: to compare the expression of immune-related genes in human PBMCs following NKT-cell activation with alpha-galactosylceramide, MAIT-cell activation with 5-amino-6-d-ribitylaminouracil/Methyl glyoxal, and V[gamma]9V[delta]2 T-cell activation with Bromohydrin pyrophosphate (BrHPP).
2021-09-30 | GSE184313 | GEO
Project description:STAT1 gain-of-function (GOF) is a primary immunodeficiency typically characterized by chronic mucocutaneous candidiasis (CMC), recurrent respiratory infections and autoimmunity. Less commonly, also immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX)-like syndromes with CMC, and combined immunodeficiency without CMC have been described. Recently, our group and others have shown that different mutation-specific mechanisms underlie STAT1 GOF in vitro, including faster nuclear accumulation (R274W), and reduced mobility (R321, N574I) to near immobility in the nucleus (T419R) upon IFNγ stimulation. In this work, we evaluated the transcriptomic fingerprint of the aforementioned STAT1 GOF mutants (R274W, R321S, T419R, and N574I) relative to STAT1 wild-type upon IFNγ stimulation in an otherwise isogenic cell model. The majority of genes up-regulated in wild-type STAT1 cells were significantly more up-regulated in cells expressing GOF mutants, except for T419R. In addition to the common interferon regulated genes (IRG), STAT1 GOF mutants up-regulated an additional set of genes, that were in part shared with other GOF mutants or mutation-specific. Overall, R274W and R321S transcriptomes clustered with STAT1 WT, while T419R and N574I had a more distinct fingerprint. We observed reduced frequency of canonical GAS sequences in promoters of genes up-regulated by all the STAT1 GOF mutants, suggesting loss of DNA binding specificity for the canonical GAS consensus. Interestingly, the T419R mutation, expected to directly increase the affinity for DNA, showed the most pronounced effects on the transcriptome. T419R STAT1 dysregulated more non-IRG than the other GOF mutants and fewer GAS or degenerate GAS promotor sequences could be found in the promoter regions of these genes. In conclusion: our work confirms hyperactivation of common sets of IFNγ-induced genes in STAT1 GOF with additional dysregulation of mutation-specific genes, in line with the earlier observed mutation-specific mechanisms. Binding to more degenerate GAS sequences is proposed as a mechanism towards transcriptional dysregulation in R274W, R321S, and N574I. For T419R, an increased interaction with the DNA is suggested to result in a broader and less GAS-specific response. Our work indicates that multiple routes leading to STAT1 GOF are associated with common and private transcriptomic fingerprints, which may contribute to the phenotypic variation observed in vivo.
2021-02-09 | GSE166392 | GEO
Project description:STAT1 is an important regulator of NK cell maturation and cytotoxicity. Although the consequences of Stat1-deficiency have been described in detail the underlying molecular functions of STAT1 in NK cells are only partially understood. Here we describe a novel non-canonical role of STAT1 that was unmasked in NK cells expressing Stat1-Y701F. This mutation prevents JAK-dependent phosphorylation, subsequent nuclear translocation and cytokine-induced transcriptional activity. As expected Stat1-Y701F mice displayed impaired NK cell maturation comparable to Stat1-/- animals. In contrast Stat1-Y701F NK cells exerted a significantly enhanced cytotoxicity in vitro and in vivo suggesting a so-far unknown cytoplasmic function. Using immunofluorescence technology we uncovered the recruitment of STAT1 to the immunological synapse during NK cell killing. A Stat1ind mouse expressing FLAG-tagged STAT1α was used to study the STAT1α interactome in NK cells. Mass spectrometry revealed that STAT1 directly binds proteins involved in cell junction formation and proteins associated to membrane or membrane-bound vesicles. We propose a novel function for STAT1 in the immunological synapse of NK cells regulating tumor surveillance and cytotoxicity.
2016-10-07 | PXD002206 | Pride
Project description:Periostin, a matricellular protein, has been reported to be important in supporting tumor cell dissemination. However, the molecular mechanisms underlying periostin function within the tumor microenvironment are poorly understood. In this study, we observe that loss of periostin decreases esophageal squamous cell carcinoma (ESCC) tumor growth in vivo and demonstrate that periostin cooperates with a conformational missense p53 mutation to enhance invasion. Pathway analyses reveal that invasive esophageal cells expressing periostin and p53R175H mutation display activation of signal transducer and activator of transcription 1 (STAT1) target genes, suggesting that the induction of STAT1 and STAT1-related genes could foster a permissive microenvironment that facilitates invasion of esophageal epithelial cells into the extracellular matrix (ECM). Genetic knockdown of STAT1 in transformed esophageal epithelial cells underscores the importance of STAT1 in promoting invasion and potentiate tumor resistance to genotoxic stress. Furthermore, we find that STAT1 is activated in ESCC xenograft tumors but this activation is attenuated with inducible knockdown of periostin in ESCC tumors. Overall, these results highlight the molecular mechanisms supporting the capacity of periostin in mediating tumor invasion during ESCC development. Pre-clinical study hTERT: EPC cells immortalized by expression of hTERT hTERT_p53: EPC cells expressing hTERT and mutant P53 hTERT_p53_POSTN: EPC cells expressing hTERT, mutant P53, and POSTN.
2016-06-01 | E-GEOD-48999 | biostudies-arrayexpress