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accession-icon GSE78718
Expression Profiling of Extracellular Microvesicles Reveals Intercellular Transmission of Oncogenic Pathways
  • organism-icon Homo sapiens
  • sample-icon 10 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Circulating microvesicles (MVs) have been described as important players in cell-to-cell communication carrying biological information both in normal and pathologic condition. MVs released by cancer cells may incorporate biomolecules such as active lipids, proteins and RNA, which can be delivered and internalized by recipient cells potentially altering gene expression of receiving cells eventually impacting disease progression. In this study, we took advantage of a leukemia in vitro model to investigate MVs as vehicles of protein coding messages. Leukemic cell lines (K562, REH and SHI-1) carrying recurrent translocations were analyzed. In the leukemic cells these translocations are transcribed into oncogenic fusion transcripts. Here, using gene expression microarrays we monitored leukemic fusion transcripts as hallmarks of leukemic cells transcriptome to track mRNA transfer from parental cells to MVs. Transcriptome analysis of K562 cells and released MVs disclosed MVs as not just small scale cells. In fact, a number of transcripts related to membrane activity, cell surface receptors and extracellular communication were enriched in the MVs pool. On the other hand, sets of transcripts related to the basal cellular functions and transcripts of the BCR-ABL oncogenic pathway downstream of the fusion protein were detected in MVs as well as in parental K562 cells. Moreover, through co-culture analyses uptake of leukemic MVs in receiving cells was confirmed and an MV-dosage dependent increase of target cell proliferation was demonstrated.

Publication Title

Expression Profiling of Circulating Microvesicles Reveals Intercellular Transmission of Oncogenic Pathways.

Sample Metadata Fields

Cell line

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accession-icon GSE75461
Pediatric AML classification according to C/EBP expression
  • organism-icon Homo sapiens
  • sample-icon 85 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Transcriptome Array 2.0 (hta20)

Description

We examined if pediatric AMLs rank-ordered according to C/EBP expression showed the activation of similar pathways. AML samples were dichotomized into groups including the upper quartile (Q1) and the lower three quartiles (Q2-4) according to their C/EBP expression values. Moreover, AML samples were associated to French-American-British (FAB) classification.

Publication Title

CREB engages C/EBPδ to initiate leukemogenesis.

Sample Metadata Fields

Specimen part, Disease

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accession-icon GSE71270
Creb overexpression induces leukemia in zebrafish by blocking myeloid differentiation process
  • organism-icon Danio rerio
  • sample-icon 10 Downloadable Samples
  • Technology Badge Icon Affymetrix Zebrafish Genome Array (zebrafish)

Description

To examine the role of CREB overexpression in hematopoiesis, we created a model of leukemia in zebrafish by overexpressing the human CREB in the myeloid hematopoietic lineage. Whole transcriptome analysis of kidney-marrow revealed 171 genes differently expressed between CREB- and control-zebrafish (five per group). Interestingly, the integration of this signature with human deposited data revealed that this tumor resembled a human AML at transcriptome level.

Publication Title

CREB engages C/EBPδ to initiate leukemogenesis.

Sample Metadata Fields

Specimen part

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accession-icon GSE79110
Zinc finger protein 521 overexpression is a feature of MLL-rearranged acute myeloid leukemia and contributes to the maintenance of myeloid differentiation block
  • organism-icon Homo sapiens
  • sample-icon 5 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

ZNF521 is a multiple zinc finger transcription factor previously identified because abundantly and selectively expressed in normal CD34+ hematopoietic stem and progenitor cells. From microarray datasets, aberrant expression of ZNF521 has been reported in both pediatric and adult acute myeloid leukemia (AML) patients with MLL gene rearrangements. However, a proper validation of microarray data is lacking, likewise ZNF521 contribution in MLL-rearranged AML is still uncertain. In this study, we show that ZNF521 is significantly upregulated in MLL translocated AML patients from a large pediatric cohort, regardless of the type of MLL translocations such as MLL-AF9, MLL-ENL, MLL-AF10 and MLL-AF6 fusion genes. Our in vitro functional studies demonstrate that ZNF521 play a critical role in the maintenance of the undifferentiated state of MLL-rearranged cells. Furthermore, analysis of the ZNF521 gene promoter region shows that ZNF521 is a direct downstream target of both MLL-AF9 and MLL-ENL fusion proteins. Gene expression profiling of MLL-AF9-rearranged THP-1 cells after depletion of ZNF521 reveals correlation with several expression signatures including stem cell-like and MLL fusion dependent programs. These data suggest that MLL fusion proteins activate ZNF521 expression to maintain the undifferentiated state and contribute to leukemogenesis.

Publication Title

ZNF521 sustains the differentiation block in MLL-rearranged acute myeloid leukemia.

Sample Metadata Fields

Specimen part, Cell line

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accession-icon GSE7896
S1P mediates key targets associated with survival, proliferation and pluripotency in human embryonic stem cells
  • organism-icon Homo sapiens
  • sample-icon 8 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Human embryonic stem cells (hESCs) replicate by the process of self-renewal, whilst maintaining their pluripotency. Understanding the pathways involved in the regulation of this self-renewal process will assist in developing fully-defined conditions for the proliferation of hESCS required for therapeutic applications. We previously demonstrated a role for Sphingosine-1-phosphate (S1P) in the survival and proliferation of hESCs. The present study investigates further key signalling pathways and the downstream targets of S1P.

Publication Title

Sphingosine-1-phosphate mediates transcriptional regulation of key targets associated with survival, proliferation, and pluripotency in human embryonic stem cells.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE59054
Detailed localisation of diet-induced changes in gene expression in the murine small intestine.
  • organism-icon Mus musculus
  • sample-icon 114 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.1 ST Array (mogene11st)

Description

An increasing amount of evidence suggests that the small intestine may play an important role in the development of metabolic diseases, such as obesity and insulin resistance. The small intestine provides the first barrier between diet and the body. As a result, dysregulation of biological processes and secretion of signal molecules from the small intestine may be of importance in the regulation and dysregulation of whole body metabolic homeostasis. Changes in gene expression of genes involved in lipid metabolism, cell cycle and immune response may contribute to the aetiology of diet-induced obesity and insulin resistance. In the current study we present a detailed investigation on the effects a chow diet, low fat diet and high fat diet on gene expression along the proximal-to-distal axis of the murine small intestine. The reported results provide a knowledge base for upcoming studies on the role of the small intestine in the aetiology of diet-induced diseases.

Publication Title

Cross-species comparison of genes related to nutrient sensing mechanisms expressed along the intestine.

Sample Metadata Fields

Sex, Specimen part

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accession-icon GSE46317
Drosophila CNS glial microarray
  • organism-icon Drosophila melanogaster
  • sample-icon 9 Downloadable Samples
  • Technology Badge Icon Affymetrix Drosophila Genome 2.0 Array (drosophila2)

Description

Gliogenesis in the Drosophila CNS occurs during embryogenesis and also during the postembryonic larval stages. Several glial subtypes are generated in the postembryonic CNS through the proliferation of differentiated glial cells. The genes and molecular pathways that regulate glial proliferation in the postembryonic CNS are poorly understood. In this study we aimed to use gene expressing profiling of CNS tissue enriched in glia to identify genes expressed in glial cells in the postembryonic CNS.

Publication Title

Glial enriched gene expression profiling identifies novel factors regulating the proliferation of specific glial subtypes in the Drosophila brain.

Sample Metadata Fields

Specimen part

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accession-icon GSE13411
Gene expression by human splenic B-cell subsets
  • organism-icon Homo sapiens
  • sample-icon 8 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133A Array (hgu133a)

Description

Enhanced secondary Ab responses are a vital component of adaptive immunity, yet little is understood about the intrinsic and extrinsic regulators of nave and memory B cells that results in differences in their responses to Ag. Microarray analysis, together with surface and intracellular phenotyping, revealed that memory B cells have increased expression of members of the TNF receptor, SLAM, B7 and Bcl2 families, as well as the TLR-related molecule CD180 (RP105). Accordingly, memory B cells exhibited enhanced survival, proliferation and Ig secretion, as well as entered division more rapidly than nave B cells in response to both T-dependent and T-independent stimuli. Furthermore, both IgM and isotype switched memory B cells, but not nave B cells, co-stimulated CD4+ T cells in vitro through a mechanism dependent on their constitutive expression of CD80 and CD86. This study demonstrates that upregulation of genes involved in activation, co-stimulation and survival provides memory B cells with a unique ability to produce enhanced immune responses and contributes to the maintenance of the memory B cell pool.

Publication Title

Resting human memory B cells are intrinsically programmed for enhanced survival and responsiveness to diverse stimuli compared to naive B cells.

Sample Metadata Fields

Specimen part

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accession-icon GSE26928
Human peripheral blood CD4+ T cell subsets
  • organism-icon Homo sapiens
  • sample-icon 8 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Cells were isolated from healthy human donors (n=2). Unstimulated cells. Cells were stained with CD4, CD45RA, CCR7 and CXCR7. Using flow cytometry, 4 CD4+ T cell populations were sorted: (1) Nave (CD45RA+CCR7+CXCR5-), (2) Central memory (CD45RA-CCR7+CXCR5-), (3) Effector memory (CD45RA-CCR7-CXCR5-) and (4) CXCR5+ cells (CD45RA-CCR7-CXCR5+)

Publication Title

CXCR5 expressing human central memory CD4 T cells and their relevance for humoral immune responses.

Sample Metadata Fields

Specimen part

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accession-icon GSE10091
Transcript-specific translational regulation in the unfolded protein response of Saccharomyces cerevisiae
  • organism-icon Saccharomyces cerevisiae
  • sample-icon 4 Downloadable Samples
  • Technology Badge Icon Affymetrix Yeast Genome S98 Array (ygs98)

Description

The accumulation of unfolded proteins in the lumen of the endoplasmic reticulum (ER) causes stress and induces the unfolded protein response (UPR) which is characterised in part by the transcriptional induction of genes involved in assisting protein folding. Translational responses to ER stress have been less well described and here we report on a genome-wide analysis of translational regulation in the response to the ER stress-inducing agent dithiothreitol (DTT) in Saccharomyces cerevisiae. Although the observed polysome profiles were similar under control and ER stress conditions microarray analysis identified transcipt-specific translational regulation. Genes with functions in ribosomal biogenesis and assembly were translationally repressed under ER stress. In contrast mRNAs for known UPR genes, including the UPR transcription factor HAC1, the ER-oxidoreductase ERO1 and the ER-associated protein degradation (ERAD) gene DER1 were enriched in polysomal fractions under ER stress conditions. In addition, we show that splicing of HAC1 mRNA is required for efficient ribosomal loading and that Gcn2p is required for normal HAC1 splicing, so shedding light on the role of this protein kinase in the UPR pathway.

Publication Title

Transcript-specific translational regulation in the unfolded protein response of Saccharomyces cerevisiae.

Sample Metadata Fields

No sample metadata fields

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refine.bio is a repository of uniformly processed and normalized, ready-to-use transcriptome data from publicly available sources. refine.bio is a project of the Childhood Cancer Data Lab (CCDL)

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Cite refine.bio

Casey S. Greene, Dongbo Hu, Richard W. W. Jones, Stephanie Liu, David S. Mejia, Rob Patro, Stephen R. Piccolo, Ariel Rodriguez Romero, Hirak Sarkar, Candace L. Savonen, Jaclyn N. Taroni, William E. Vauclain, Deepashree Venkatesh Prasad, Kurt G. Wheeler. refine.bio: a resource of uniformly processed publicly available gene expression datasets.
URL: https://www.refine.bio

Note that the contributor list is in alphabetical order as we prepare a manuscript for submission.

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