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Single cell RNA-seq analysis of normal, premalignant state and tumor mouse models of VAV1-MYOF gene fusion in Peripheral T-Cell Lymphoma

ABSTRACT: The goal of this study is to identify transcriptomic effects of VAV1-MYOF expression in mouse CD4+ T lymphocytes and tumor progression in TET2KO and TET2WT backgrounds. To this end, mice conditionally expressing VAV1-MYOF were crossed with the CD4CreERT2 line or CD4-Cre, under the control of the mouse Cd4 promoter to generate CD4 specific VAV1-MYOF models. In inducible models, mice were treated with vehicle only or Tamoxifen to induce expression of VAV1-MYOF1 in CD4+ T cells. Mice were crossed with CD4-CreERT2 Tet2f/f to obtain the experimental phenotypes. Whole spleen samples were processed and single cell suspensions were analyzed using scRNA-seq technologies.

ORGANISM(S): Mus musculus

PROVIDER: GSE166672 | GEO | 2021/05/12

REPOSITORIES: GEO

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Bulk transcriptomic analysis of normal, premalignant state and tumor mouse models of VAV1-MYOF gene fusion in Peripheral T-Cell Lymphoma

Project description:The goal of this study is to identify transcriptomic effects of VAV1-MYOF expression in mouse CD4+ T lymphocytes in tumor development as well as changes in the microenvironment. To this end, mice conditionally expressing VAV1-MYOF were crossed with the CD4CreERT2 line or CD4-Cre, under the control of the mouse Cd4 promoter to generate CD4 specific VAV1-MYOF models. In inducible models, mice were treated with vehicle only or Tamoxifen to induce expression of VAV1-MYOF1 in CD4+ T cells. CD4CreERT2 mice were included as a negative control. Total RNA was extracted from whole spleen samples or CD4+ T cells isolated by single cell suspensions of spleen by negative selection using the mouse naive CD4+ T Cell Isolation Kit (Milteny#130-104-453) according to the manufacturer’s protocol. Standard Illumina poly-A RNA seq was performed.

2021-05-12 | GSE166671 | GEO

Analysis of the Vav1 interactome in primary T cells

Project description:In this study, we combined mouse genetics and quantitative proteomics to characterize in a comprehensive manner the VAV1 interactome. A line of knock-in mouse expressing endogenous VAV1 molecules with a genetic tag permitting affinity purification was generated and combined with affinity purification and mass spectrometry (AP-MS) to analyze the VAV1 signaling complex that assembles in primary CD4+ T cells over 300 s of activation. This allowed us to describe in a time-resolved manner the interactome of VAV1 in primary CD4+ T cells and to identify 44 previously unknown bindings partners of VAV1. The dataset contains mass spectrometry results from the analysis of AP-MS purifications (based on affinity purification on Streptactin beads of One-Strep-tagged proteins) starting from CD4+ T cells which were either non stimulated or stimulated with pervanadate for different time lengths. Control samples for each time point were prepared from wild-type mice. 8 different conditions were thus analyzed: - VAV1-OST transgenic mice, CD4+ T cells non stimulated (noted Vav_0) - VAV1-OST transgenic mice, CD4+ T cells stimulated 30s (noted Vav_30) - VAV1-OST transgenic mice, CD4+ T cells stimulated 120s (noted Vav_120) - VAV1-OST transgenic mice, CD4+ T cells stimulated 300s (noted Vav_300) - WT mice, CD4+ T cells non stimulated (noted WT_0) - WT mice, CD4+ T cells stimulated 30s (noted WT_30) - WT mice, CD4+ T cells stimulated 120s (noted WT_120) - WT mice, CD4+ T cells stimulated 300s (noted WT_300) Four biological replicates were prepared for these 8 different conditions (noted S1, S2, S3, S4), yielding 32 analyzed samples. Three technical nanoLC-MS runs were acquired for each sample (noted R1, R2, R3), except for some samples of the biological series S4 for which 2 technical nanoLC-MS runs were performed. This led to 91 nanoLC-MS raw files composing the dataset.

2018-06-26 | PXD004217 | Pride

Genome-wide analysis of gene expression in VAV1-/- versus VAV1+/+ bone marrow (BM)-macrophages

Project description:Analysis of differential gene expression profiles in VAV1-/- versus VAV+/+ BM-macrophages , respectively. A distinct expression profile in VAV1-/- versus VAV1+/+ (wild-type) BM-macrophages allows to resolve molecular mechanisms. Total RNA was obtained froms BM-macrophages of VAV1+/+ and VAV1-/- mice

2013-03-08 | E-GEOD-36123 | biostudies-arrayexpress

Genome-wide analysis of gene expression in VAV1-/- versus VAV1+/+ bone marrow (BM)-macrophages

2013-03-08 | GSE36123 | GEO

Bulk transcriptomic analysis of normal, premalignant state and tumor mouse models of VAV1-MYOF gene fusion in Peripheral T-Cell Lymphoma

Project description:Bulk transcriptomic analysis of normal, premalignant state and tumor mouse models of VAV1-MYOF gene fusion in Peripheral T-Cell Lymphoma

| PRJNA701570 | ENA

Cancer-associated mutations in VAV1 trigger variegated signaling outputs and drive T cell lymphomagenesis

Project description:Mutations in VAV1, a multifunctional signaling protein essential for T lymphocytes, have been recently found in peripheral T cell lymphoma (PTCL) and other tumors. However, their pathobiological significance remains unsettled. Here, we show that these mutations belong to several subclasses according to the spectra of VAV1 signaling branches deregulated by them. These mutations target both known and new regulatory hotspots as well as transitional activation states of the protein. The most frequent VAV1 mutant subclass drives PTCL formation in mice by exacerbating normal VAV1- dependent signaling responses in follicular helper T cells.

2021-09-01 | GSE165006 | GEO

Single cell RNA-seq analysis of normal, premalignant state and tumor mouse models of VAV1-MYOF gene fusion in Peripheral T-Cell Lymphoma

Project description:Single cell RNA-seq analysis of normal, premalignant state and tumor mouse models of VAV1-MYOF gene fusion in Peripheral T-Cell Lymphoma

| PRJNA701571 | ENA

EXPRESSION OF VAV1 IN GLIOBLASTOMA MULTIFORME

Project description:Background: Even though much progress has been made in the understanding of the molecular nature of glioma, the survival rates of patients affected of this tumour have not changed significantly during these years. Thus, a deeper understanding of this malignancy is still needed in order to predict its outcome and improve patient treatment. Here, we report that VAV1, a GDP/GTP exchange factor for Rho/Rac proteins with oncogenic potential that is involved in the regulation of cytoskeletal dynamics and cell migration. Methodology/Principal Findings: VAV1 is overexpressed in 32 patients diagnosed with high-grade glioma. Such overexpression is linked to the parallel upregulation of a number of genes coding for proteins also involved in cell invasion- and migration-related processes. Unexpectedly, immunohistochemical experiments revealed that VAV1 is not expressed in glioma cells. Instead, VAV1 is found in non-tumoral astrocyte-like cells that are located either peritumoraly or perivascularly, suggesting that its expression is linked to synergistic signalling cross-talk between cancer and infiltrating cells. Conclusions/Significance: Interestingly, we show that the pattern of expression of VAV1 is a good prognostic factor to unveil populations of high-grade glioma patients with different survival and progression free survival rates.

2010-09-30 | GSE24072 | GEO

Characterization of the spectrum of trivalent VAV1 mutation-driven tumors using a gene-edited mouse model

Project description:VAV1 mutations have been recently found in peripheral T cell lymphoma and non-small cell lung cancer. To understand their pathogenic potential, we generated a gene-edited mouse model that expresses a Vav1 mutant protein that recapitulates the signaling alterations present the VAV1 mutant subclass most frequently found in tumors. We could not detect any overt tumorigenic process in those mice. However, the concurrent elimination of the Trp53 tumor suppressor gene in them drives T cell lymphomagenesis. This process represents an exacerbation of the normal functions that wild-type Vav1 plays in follicular helper T cells. We also found that, in combination with an oncogenic Kras mutation, the Vav1 mutant version favors progression of non-small cell lung cancer. These data indicate that VAV1 mutations play critical, although highly cell typespecific roles in tumorigenesis. They also indicate that such functions are contingent on the mutational landscape of the tumors involved.

2022-10-12 | GSE189221 | GEO

Protein Arginine Methyltransferase 1 is Essential for the Meiosis of Male Germ Cells

Project description:Methods: Prmt1 floxed mice were crossed with Rip2-Cre and Pdx1-CreERT2 mice to generate Prmt1 KO and Prmt1 iKO mice. R26-eYFP mice were crossed for lineage tracing experiments and cell sorting. All mice were backcrossed and maintained on a C57BL/6J background. Cre recombination for CreERT2 was induced by total 5 times intraperitoneal injections (75 mg/kg) of corn oil dissolved tamoxifen (T5648, Sigma-Aldrich) over 2 weeks.

2021-08-11 | GSE176443 | GEO

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