The RPMI-8226 human multiple myeloma cell line was stably infected with either a validated shRNA against BMI1 or a control shRNA. RNA was prepared from these lines, +/- doxycycline induction and at various time points post-induction. Samples were hybridized on the Affymetrix U133plus2 human genome expression microarray.
The Polycomb group protein Bmi-1 is essential for the growth of multiple myeloma cells.
Cell line
View SamplesWe report a comprehensive large-scale expression profiling analysis of mammalian male germ cells undergoing mitotic growth, meiosis and gametogenesis using High Density Oligonucleotide Microarrays and highly enriched cell populations. Among 11955 rat loci investigated, 1268 were identified as differentially transcribed in germ cells at subsequent developmental stages as compared to total testis, somatic Sertoli cells as well as brain and skeletal muscle controls. The loci were organized into four expression clusters that correspond to somatic, mitotic, meiotic and post-meiotic cell types. This work provides information about expression patterns of approximately 200 genes known to be important during male germ cell development. Approximately 40 of those are included in a group of 121 transcripts for which we report germ cell expression and lack of transcription in three somatic control cell types. Moreover, we demonstrate the testicular expression and transcriptional induction in mitotic, meiotic and/or post-meiotic germ cells of 293 as yet uncharacterized transcripts some of which are likely to encode factors involved in spermatogenesis and fertility. This group also contains numerous potential germ cell specific targets for innovative contraceptives. A graphical display of the data is conveniently accessible through the GermOnline database at <a href="http://www.germonline.org" target="_blank">http://www.germonline.org</a>.
Expression profiling of mammalian male meiosis and gametogenesis identifies novel candidate genes for roles in the regulation of fertility.
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Plasmacytoid dendritic cells and C1q differentially regulate inflammatory gene induction by lupus immune complexes.
Specimen part, Treatment, Subject
View SamplesThe goal of this study was to determine what genes are up- and down-regulated in response to lupus immune complexes in purified CD14+ monocyte stimulations. Our results have shown that novel genes are induced by immune complexes but the response is less robust when using purified monocytes versus total PBMCs
Plasmacytoid dendritic cells and C1q differentially regulate inflammatory gene induction by lupus immune complexes.
Specimen part, Treatment, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Identification of a novel gene for diabetic traits in rats, mice, and humans.
Sex, Age, Specimen part
View SamplesUsing heterogeneous stock (HS) rats, we have identified a region on rat chromosome 1 that maps multiple diabetic traits. We sought to use global expression analysis to determine if genes within this region are differentially expressed between HS rats with normal glucose tolerance and those with glucose intolerance
Identification of a novel gene for diabetic traits in rats, mice, and humans.
Sex, Age, Specimen part
View SamplesBmi-1 and Mel-18 are close structural homologues that belong to the polycomb group (PcG) of transcriptional regulators of homeotic gene expression in development. They are believed to stably maintain repression of gene expression by altering the state of chromatin at specific promoters. A number of clinical and experimental observations have also implicated Bmi-1 in tumorigenesis and stem cell maintenance. Bmi-1 overexpression or amplification has been observed in a number of human malignancies, particularly in B-cell lymphomas, medulloblastomas and breast cancer. We report here that shRNA-mediated knock-down of either Bmi-1 or Mel-18 in human medulloblastoma DAOY cells results in the inhibition of proliferation, loss of clonogenic survival and anchorage-independent growth, and suppression of xenograft tumor formation in nude mice. Furthermore, overexpression of both Bmi-1 and Mel-18 significantly increased clonogenic survival of Rat1 fibroblasts. In contrast, stable downregulation of Bmi-1 or Mel-18 alone did not affect the growth of SK-OV-3 or U2OS cancer cell lines or normal human WI38 fibroblasts. Gene expression analysis of shRNA-expressing DAOY cells has demonstrated a significant overlap in the Bmi-1- and Mel-18-regulated genes and revealed novel gene targets under their control. Taken together, these results suggest that Bmi-1 and Mel-18 might have overlapping functions in human tumorigenesis.
Contribution of polycomb homologues Bmi-1 and Mel-18 to medulloblastoma pathogenesis.
No sample metadata fields
View SamplesIn most embryos, the mid-blastula transition is a complex process featuring maternal RNA degradation, cell cycle pause, zygotic transcriptional activation and morphological changes. The nucleocytoplasmic (N/C) ratio has been proposed to control the multiple events at MBT. To understand the global transcriptional response to the changes of the N/C ratio, we profiled wild type and haploid embryos using cDNA microarrays at three developmental stages.
Coupling of zygotic transcription to mitotic control at the Drosophila mid-blastula transition.
No sample metadata fields
View SamplesKaposis sarcoma-associated hepesvirus (KSHV) encodes four genes with homology to human interferon regulatory factors (IRFs). One of these IRFs, the viral interferon regulatory factor 3 (vIRF-3) is expressed in latently infected PEL cells and required for their continuous proliferation. Moreover, vIRF-3 is known to be involved in modulation of the type I interferon response.
Kaposi's sarcoma-associated herpesvirus viral interferon regulatory factor 3 inhibits gamma interferon and major histocompatibility complex class II expression.
Specimen part, Cell line
View SamplesThe Early Growth Response (Egr) family of transcription factors consists of 4 members (Egr1-4) that are expressed in a wide variety of cell types. A large body of evidence point to a role for Egr transcription factors in growth, survival, and differentiation. A major unanswered question is whether Egr transcription factors serve similar functions in diverse cell types by activating a common set of target genes. Signal transduction cascades in neurons and lymphocytes show striking parallels. Activation of either cell type activates the Ras-MAPK pathway and, in parallel, leads to increases in intracellular calcium stimulating the calcineurin-NFAT pathway. In both cell types, the strength of the activation signal affects the cellular outcomes and very strong stimuli lead to cell death. Notably both these pathways converge on the induction of Egr genes. We believe that downstream targets of Egr transcription factors in lymphocytes may also be activated by Egr factors in activated neurons. There is precedence for common target gene activation in these two cell types: apoptosis in both activated T cells and methamphetamine stimulated neurons occurs via FasL induction by NFAT transcription factors. We propose to use developing T lymphocytes (thymocytes) as a model system for discovery of Egr-dependent target genes for several reasons. First, we have observed a prominent survival defect in thymocytes from mice deficient in both Egr1 and Egr3 (1/3 DKO) and a partial differention block in the immature double negative (DN) stage. In addition, thymocytes are an easily manipulatable cell type, and the DN subpopulation affected in 1/3 DKO mice can be isolated to very high purity. We anticipate that 1/3 DKO thymocytes will provide an excellent experimental system that will provide insight into Egr-dependent transcription in neuronal development, activation, and death.
Redundant role for early growth response transcriptional regulators in thymocyte differentiation and survival.
No sample metadata fields
View Samples