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GSE89506
Drosophila melanogaster
16 Downloadable Samples
Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Blocking promiscuous activation at cryptic promoters directs cell type-specific gene expression.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 17 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
The effect of different loss of functions; kumgang (kmg or CG5204), dMi-2, and kmg and always early (aly) double on the gene expression in spermatocyte differentation was assessed by microarray.
Publication Title
Blocking promiscuous activation at cryptic promoters directs cell type-specific gene expression.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Maternal Embryonic Leucine Zipper Kinase (MELK), a Ser/Thr protein kinase, is highly over expressed in stem and cancer cells. The oncogenic role of MELK is attributed to its capacity to disable critical cell cycle checkpoints and to enhance replication. Most functional studies have relied on the use of siRNA/shRNA-mediated gene silencing, but this is often compromised by off target effects. Here we present the cellular validation of a novel, potent and selective small molecule MELK inhibitor, MELK-T1, which has enabled us to explore the biological function of MELK. Strikingly, the binding of MELK-T1 to endogenous MELK triggers a rapid and proteasome dependent degradation of the MELK protein. Treatment of MCF-7 breast adenocarcinoma cells with MELK-T1 leads to an accumulation of stalled replication forks and double strand breaks, followed by a replicative senescence phenotype. This phenotype correlates with a rapid and long-lasting ATM activation and phosphorylation of CHK2. Furthermore, MELK-T1 induces strong phosphorylation of p53 and prolonged up-regulation of p21.
Publication Title
MELK-T1, a small-molecule inhibitor of protein kinase MELK, decreases DNA-damage tolerance in proliferating cancer cells.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Human coronary smooth muscle cells were treated with two different -blocker (metoprolol and nebivolol). RNA from three replicates of each, treated and the untreated control group, were isolated and the expression profiles were determined using Affymetrix Human Genechip U133A arrays. Comparisons between the sample groups allow the identification of genes with different expression patterns between the treated and untreated control cells.
Publication Title
Major differences in gene expression in human coronary smooth muscle cells after nebivolol or metoprolol treatment.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 181 Downloadable Samples
Description
CML stem cells (CMLSCs) and normal hematopoietic stem cells (HSCs) display the same set of surface markers (CD34+CD38-CD90+CD45RA-), making it infeasible to separate these two populations within the same sample. To overcome this challenge, and to minimize variations in gene expression due to individual variation, here we perform single-cell RNA-seq to compare expression profiles of CMLSCs and HSCs isolated from the same patient. We captured ~600 HSCs (CD34+CD38-CD90+CD45RA-) (~200 from each of three CML patient samples), separated them into CMLSCs (BCR-ABL+) or normal HSCs (BCR-ABL-) based on the presence of the BCR-ABL transcript, and performed paired-end deep sequencing. Typically, we obtained ~2.5 million mapped reads (>70% average mapping efficiency) and detected ~5,000 genes (transcript per million [TPM]>1) per cell. Despite the heterogeneity of the gene expression pattern, we were able to identify genes that were significantly more highly expressed in CMLSCs than in normal HSCs. Notably, among these genes are two cell surface markers, CD33 and CD47, that could potentially be used to distinguish CMLSCs from normal HSCs. We also found genes, such as PIM2, that could be targeted for CML therapy using available small molecule inhibitors. Overall design: Hematopoietic stem cell population from three chronic phase CML patients with no detectable BCR-ABL mutation.
Publication Title
Prosurvival kinase PIM2 is a therapeutic target for eradication of chronic myeloid leukemia stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 88 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Parkinson's disease (PD) is an adult-onset movement disorder of largely unknown etiology. We have previously shown that loss-of-function mutations of the mitochondrial protein kinase PINK1 (PTEN induced putative kinase 1) cause the recessive PARK6 variant of PD. Now we generated a PINK1 deficient mouse and observed several novel phenotypes: A progressive reduction of weight and of locomotor activity selectively for spontaneous movements occurred at old age. As in PD, abnormal dopamine levels in the aged nigrostriatal projection accompanied the reduced movements. Possibly in line with the PARK6 syndrome but in contrast to sporadic PD, a reduced lifespan, dysfunction of brainstem and sympathetic nerves, visible aggregates of -synuclein within Lewy bodies or nigrostriatal neurodegeneration were not present in aged PINK1-deficient mice. However, we demonstrate PINK1 mutant mice to exhibit a progressive reduction in mitochondrial preprotein import correlating with defects of core mitochondrial functions like ATP-generation and respiration. In contrast to the strong effect of PINK1 on mitochondrial dynamics in Drosophila melanogaster and in spite of reduced expression of fission factor Mtp18, we show reduced fission and increased aggregation of mitochondria only under stress in PINK1-deficient mouse neurons. Thus, aging Pink1/ mice show increasing mitochondrial dysfunction resulting in impaired neural activity similar to PD, in absence of overt neuronal death. Transcriptome microarray data of Pink1-/- mouse brains in absence of a stressor, even at old age, show remarkably sparse dysregulations. See Gispert-S et al 2009 PLOS ONE.
Publication Title
Potentiation of neurotoxicity in double-mutant mice with Pink1 ablation and A53T-SNCA overexpression.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
RNA-seq was used to evaluate transcriptional changes in alloreactive TCR-Tg CD8 T cells during activation and tolerance induction. CBA mice were exposed to a low dose whole body irradiation and then injected with bone marrow from TCR-Tg KB5 mice to generate synchimeric mice. The KB5 TCR recognizes alloantigens from H2b MHC molecules, specifically Kb, that are expressed by C57BL/6 mice. The injection of bone marrow from KB5 mice into CBA mice enables the development of small and traceable population of TCR-Tg KB5 CD8 T cells. A clonotypic antibody specific for the KB5 TCR allows these cells to be monitored and sorted from the periphery of synchimeric mice by flow cytometry. KB5 CD8 T cells were purified by sorting cells from synchimeric mice under the following conditions: 1) not exposed to alloantigens and in a naïve state, 2) exposed to H2b antigens from C57BL/6 mice to activate the KB5 CD8 T cells, 3) exposed to H2b antigens in the presence of anti-CD154 that blocks costimulatory signals and induces transplantation tolerance, or 4) treated with alloantigens, anti-CD154 and LPS, that induces an inflammatory response and abrogates the induction of tolerance. KB5 CD8 T cells were FACS purified to a level of greater than 95%, RNA was recovered from the purified cells and RNA-seq was performed on triplicate samples from 3 independent experiments. Overall, the analyses revealed expression changes for a number of genes that regulate immune responses and inflammation, cell proliferation and immune cell homing. Overall design: Determine the changes in gene expression profiles that are induced during constimulation blockade.
Publication Title
Cutting Edge: Early Attrition of Memory T Cells during Inflammation and Costimulation Blockade Is Regulated Concurrently by Proapoptotic Proteins Fas and Bim.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Alterations in the tissue microenvironment collaborate with cell autonomous genetic changes to contribute to neoplastic progression. The importance of the microenvironment in neoplastic progression is underscored by studies demonstrating that fibroblasts isolated from a tumor stimulate the growth of preneoplastic and neoplastic cells in xenograft models. Similarly, senescent fibroblasts promote preneoplastic cell growth in vitro and in vivo. Because senescent cells accumulate with age, their presence is hypothesized to facilitate preneoplastic cell growth and tumor formation in older individuals. To identify senescent stromal factors directly responsible for stimulating preneoplastic cell growth, we carried out whole genome transcriptional profiling and compared senescent fibroblasts to their younger counterparts. We identified osteopontin (OPN) as one of the most highly elevated transcripts in senescent fibroblasts. Importantly, reduction of OPN protein levels by RNAi did not impact senescence induction in fibroblasts; however, it dramatically reduced the growth-promoting activities of senescent fibroblasts in vitro and in vivo, demonstrating that OPN is necessary for paracrine stimulation of preneoplastic cell growth. In addition, we found that recombinant OPN was sufficient to stimulate preneoplastic cell growth. Finally, we demonstrate that OPN is expressed in senescent stroma within preneoplastic lesions that arise following DMBA/TPA treatment of mice, suggesting that stromal-derived OPN-mediated signaling events impact neoplastic progression.
Publication Title
Senescent stromal-derived osteopontin promotes preneoplastic cell growth.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Progenitors in human vasculature expanded in-vitro were differentiated with adipogenic cocktail for 12 days, following which they were stimulated with forskolin for 7 days
Publication Title
Human 'brite/beige' adipocytes develop from capillary networks, and their implantation improves metabolic homeostasis in mice.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Using BCR-ABL-induced chronic myeloid leukemia (CML) as a disease model for leukemia stem cells (LSCs), we showed that BCR-ABL down-regulates the B lymphoid kinase (Blk) gene in leukemia stem cells in CML mice and that Blk functions as a tumor suppressor in LSCs and suppresses LSC function. Inhibition of this Blk pathway accelerates CML development, whereas increased activity of the Blk pathway delays CML development. To identify the pathways in which Blk regulates function of LSCs, we performed a comparative DNA microarray analysis using total RNA isolated from non-BCR-ABL-expressing Lin-Sca-1+c-Kit+, BCR-ABL- and BCR-ABL-Blk expressing LSCs. This analysis revealed a large group of candidate genes that exhibited changes in the levels of transcription in the Blk expressing LSCs, and uncovered the molecular mechanisms by which Blk suppresses LSCs and CML development.
Publication Title
The Blk pathway functions as a tumor suppressor in chronic myeloid leukemia stem cells.
Sample Metadata Fields
Age, Specimen part
View Samples