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GSE60100
Homo sapiens
20 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: The transcription factor EVI1 regulates cellular proliferation, differentiation, and apoptosis, and contributes to an aggressive course of disease in myeloid leukemias and other malignancies. Notwithstanding, knowledge about the target genes mediating its biological and pathological functions remains limited. We therefore aimed to identify and characterize novel EVI1 target genes in human myeloid cells. Methods: U937T_EVI1, a previously established human myeloid cell line expressing EVI1 in a tetracycline regulable manner, was subjected to genome wide gene expression microarray analysis. qRT-PCR was used to confirm the regulation of MS4A3 by EVI1. Reporter constructs containing various parts of the MS4A3 upstream region were employed in luciferase assays, and direct binding of EVI1 to the MS4A3 promoter was investigated by chromatin immunoprecipitation. U937 derivative cell lines experimentally expressing EVI1 and/or MS4A3 were generated by retroviral transduction, and tested for their tumorigenicity by subcutaneous injection into severe combined immunodeficient mice. Experimental results were tested for statistical significance using ANOVA and Student's t-test (two-tailed). Results: Gene expression microarray analysis identified 27 unique genes that were up-regulated and 29 that were down-regulated in response to EVI1 induction in the human myeloid cell line, U937. The most strongly repressed gene was membrane-spanning-4-domains subfamily-A member-3 (MS4A3), and its down-regulation by EVI1 was confirmed by qRT-PCR in additional, independent experimental model systems. Reporter gene assays and chromatin immunoprecipitation showed that EVI1 regulated MS4A3 via direct binding to a promoter proximal region. Experimental re-expression of MS4A3 in an EVI1 overexpressing cell line counteracted the tumor promoting effect of EVI1 in a murine xenograft model. Conclusions: Our data reveal MS4A3 as a novel direct target of EVI1 in human myeloid cells, and show that its repression plays a role in EVI1 mediated tumor aggressiveness.
Publication Title
EVI1 promotes tumor growth via transcriptional repression of MS4A3.
Sample Metadata Fields
Cell line, Time
View Samples- Mus musculus
- 36 Downloadable Samples
Illumina HiSeq 2500
Description
By conditionally deleting BRD4 at various stages of thymic differentiation, we have established that BRD4 deficiency selectively affects a unique developmental subpopulation of thymocytes. Overall design: We examined by RNA-seq the effect on gene expression of BRD4 deletion in ex vivo DN, ISP, DP, CD4 and CD8 thymocyte subpopulations. The analysis was also performed on WT or BRD4 deleted ISP and DP thymocytes cultured for 16 hours at 37oC In this analysis, the conditional deletion of BRD4 (cKO) is achieved using the LCK-cre Transgene.
Publication Title
Immature CD8 Single-Positive Thymocytes Are a Molecularly Distinct Subpopulation, Selectively Dependent on BRD4 for Their Differentiation.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 21 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
Innate immunity is fundamental to recognition and clearance of bacterial infection. The relevant cells and molecules that orchestrate an effective response, however, remain incompletely understood. Here we describe a previously unknown population of B cells, which we have named innate response activator (IRA) B cells that recognize bacteria directly through TLR-4-MyD88 and protect against polymicrobial sepsis.
Publication Title
Innate response activator B cells protect against microbial sepsis.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples