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accession-icon GSE25613
A Novel Pro-Survival Function of Cyclin-D1 Underlies Its Oncogenic Role and Potential as a Therapeutic Target in Human and Murine Mantle Cell Lymphoma
  • organism-icon Homo sapiens
  • sample-icon 19 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

The chromosomal translocation t(11;14)(q13;q32) leading to cyclin-D1 over-expression plays an essential role in the development of mantle cell lymphoma (MCL), an aggressive tumor that remains incurable with current therapies. Cyclin-D1 has been postulated as an effective therapeutic target, but its evaluation has been hampered by our incomplete understanding of its oncogenic functions and by the lack of valid MCL murine models. To address these issues, we generated a cyclin-D1-driven mouse model whereby cyclin-D1 expression can be externally regulated. These mice developed lymphomas capable of recapitulating most features of human MCL. We found that cyclin-D1 inactivation was not sufficient to induce lymphoma regression in vivo. However, using a combination of in vitro and in vivo assays, we identified a novel pro-survival cyclin-D1 function in MCL cells. Specifically, we demonstrate that cyclin-D1 sequestrates the pro-apoptotic protein BAX, thereby favoring BCL2 anti-apoptotic function. Accordingly, cyclin-D1 inhibition sensitized the lymphoma cells to apoptosis through BAX release. Thus, genetic or pharmacologic targeting of cyclin-D1 combined with a pro-apoptotic BH3 mimetic synergistically killed murine lymphomas and human MCL cells. Our study identifies a novel role of cyclin-D1 in deregulating apoptosis and highlights the potential benefit of simultaneously targeting cyclin-D1 and survival pathways in patients with MCL.

Publication Title

A cyclin-D1 interaction with BAX underlies its oncogenic role and potential as a therapeutic target in mantle cell lymphoma.

Sample Metadata Fields

Specimen part, Cell line

View Samples
accession-icon GSE42808
Expression data from human umbilical vein endothelial cells (HUVEC) treated with DMSO, telmisartan, or telmisartan and amlodipine
  • organism-icon Homo sapiens
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Gene 1.0 ST Array (hugene10st)

Description

Objective Telmisartan, an angiotensin II type 1 (AT1) receptor blocker, and amlodipine, a calcium channel blocker, are antihypertensive agents clinically used as monotherapy or in combination. They exert beneficial cardiovascular effects independently of blood pressure lowering and classic mechanisms of action. In this study, we investigate molecular mechanisms responsible for the off-target effects of telmisartan and telmisartan-amlodipine in endothelial cells (EC), using an unbiased approach.

Publication Title

Telmisartan exerts pleiotropic effects in endothelial cells and promotes endothelial cell quiescence and survival.

Sample Metadata Fields

Specimen part, Disease, Treatment

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accession-icon GSE45564
Expression data in the presence of miR-29a inhibition in human dermal fibroblast cells
  • organism-icon Homo sapiens
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Gene 1.0 ST Array (hugene10st)

Description

miR-29 can target many gene transcripts encoding extracellular matrix proteins. To unravel novel targets, we used microarray analysis to detect global gene expression changes when inhibiting endogenous miR-29.

Publication Title

Ten-eleven translocation (Tet) and thymine DNA glycosylase (TDG), components of the demethylation pathway, are direct targets of miRNA-29a.

Sample Metadata Fields

Specimen part, Treatment

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accession-icon GSE11103
Study of human immune and memory T cells using microarray
  • organism-icon Homo sapiens
  • sample-icon 39 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

Deconvolution of blood microarray data identifies cellular activation patterns in systemic lupus erythematosus.

Sample Metadata Fields

Specimen part, Disease

View Samples
accession-icon GSE11057
Memory T Cell Subsets
  • organism-icon Homo sapiens
  • sample-icon 16 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Microarray deconvolution is a technique for quantifying the relative abundance of constituent cells in a mixture based on that mixture's microarray signature and the signatures of the purified constituents. It has been applied to yeast and other systems but not to blood samples.

Publication Title

Deconvolution of blood microarray data identifies cellular activation patterns in systemic lupus erythematosus.

Sample Metadata Fields

Specimen part, Disease

View Samples
accession-icon GSE11058
Immune Cell Line Mixtures
  • organism-icon Homo sapiens
  • sample-icon 16 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Microarray deconvolution is a technique for quantifying the relative abundance of constituent cells in a mixture based on that mixture's microarray signature and the signatures of the purified constituents. Its ability to discriminate related human cells is unknown.

Publication Title

Deconvolution of blood microarray data identifies cellular activation patterns in systemic lupus erythematosus.

Sample Metadata Fields

No sample metadata fields

View Samples
accession-icon SRP099018
Single cell RNA expression of mouse embryonic basal forebrain
  • organism-icon Mus musculus
  • sample-icon 225 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2500

Description

Single-cell RNA-Seq RNA from medial ganglionic eminence at E11.5, E13.5, E15.5 or E17.5. The ID of this project in Genentech''s ExpressionPlot database is PRJ0007389 Overall design: Single-cell RNA-Seq from medial ganglionic eminence at E11.5, E13.5, E15.5 or E17.5.

Publication Title

Single-cell RNA sequencing identifies distinct mouse medial ganglionic eminence cell types.

Sample Metadata Fields

Specimen part, Subject

View Samples
accession-icon SRP098938
Embryonic stem cells-derived neural progenitor cells
  • organism-icon Mus musculus
  • sample-icon 140 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2500

Description

J14 ES cells differentiated into MGE-like cells. Three groups of single-cell preparations were analyzed: ES cells (undifferentiated), differentiated cells (unsorted, of which less than 10% are GFP+) and GFP+ differentiated cells. These are specified in the "group" sample characteristic, with values "ES", "Unsorted" and "GFP+" respectively. The "SAMPLE_ID" sample characteristic is a sample identifier internal to Genentech. The ID of this project in Genentech''s ExpressionPlot database is PRJ0007904 Overall design: J14 ES cells differentiated into MGE-like cells

Publication Title

Single-cell RNA sequencing identifies distinct mouse medial ganglionic eminence cell types.

Sample Metadata Fields

Cell line, Subject

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accession-icon GSE30956
Expression data from pig BMDM treated with salmonella LPS
  • organism-icon Sus scrofa
  • sample-icon 22 Downloadable Samples
  • Technology Badge Icon Affymetrix Porcine Genome Array (porcine)

Description

Mouse bone marrow-derived macrophages (BMDM) grown in macrophage colony-stimulating factor (CSF-1) have been used widely in studies of macrophage biology and the response to toll-like receptor agonists. We investigated whether similar cells could be derived from the domestic pig. Cultivation of pig bone marrow cells for 5-7 days in presence of rhCSF-1 generated a pure population of BMDM that expressed the usual macrophage markers (CD14, CD16, CD163, CD172a), are potent phagocytic cells and produced tumor necrosis factor (TNF) in response to lipopolysaccharide (LPS). Bone marrow cells could be stored frozen and thawed, providing a renewable resource.

Publication Title

Pig bone marrow-derived macrophages resemble human macrophages in their response to bacterial lipopolysaccharide.

Sample Metadata Fields

Sex, Specimen part, Time

View Samples
accession-icon GSE12956
Arx acts as a key selector gene of the ventral telencephalon mainly through its repression transcriptional activity
  • organism-icon Mus musculus
  • sample-icon 10 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

The homeobox containing gene Arx is expressed during ventral telencephalon development and it is required for correct GABAergic interneuron tangential migration from the ganglionic eminences to the olfactory bulbs, cerebral cortex and striatum. Its human ortholog is associated with a variety of neurological clinical manifestations whose syntoms are compatible with a loss of cortical interneurons and altered basal ganglia related-activities in humans. Herein, we reported the identification by global expression profiling of a group of genes whose expression is consistently altered in Arx mutant ganglionic eminences. Following analysis revealed the striking ectopic expression in the ganglionic eminences of a number of genes normally not, or only marginally, expressed in the ventral telencephalon. Among them, we functionally analyzed Ebf3, whose ectopic expression in ventral telencephalon is preventingneuronal tangential migration. Further, we showed that Arx is sufficient to repress Ebf3 endogenous expression and that its silencing in Arx mutant tissue might marginally rescue tangential cell movements. Together, these data provide an initial analysis of the molecular pathways regulated by Arx and how their networking might regulate those specific cellular processes during telencephalon development strongly altered by loss of Arx.

Publication Title

Arx acts as a regional key selector gene in the ventral telencephalon mainly through its transcriptional repression activity.

Sample Metadata Fields

No sample metadata fields

View Samples
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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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Developed by the Childhood Cancer Data Lab

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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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