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accession-icon GSE74181
Brg1 Coordinates Multiple Processes During Retinogenesis and is a Tumor Suppressor in Retinoblastoma
  • organism-icon Mus musculus
  • sample-icon 46 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

Retinal development requires precise temporal and spatial coordination of cell cycle exit, cell-fate specification, cell migration and differentiation. When this process is disrupted, retinoblastoma, a developmental tumor of the retina, can form. Epigenetic modulators are central to precisely coordinating developmental events, and many epigenetic processes have been implicated in cancer. Studying epigenetic mechanisms in development is challenging because they often regulate multiple cellular processes; therefore, elucidating the primary molecular mechanisms involved can be difficult. Here we explore the role of Brg1 in retinal development and retinoblastoma by using molecular and cellular approaches. Brg1 regulated retinal size by controlling cell cycle length, cell cycle exit, and cell survival during development. Brg1 was not required for cell-fate specification but was required for photoreceptor differentiation and cell adhesion/polarity programs that contribute to proper retinal lamination during development. The combination of defective cell differentiation and lamination led to retinal degeneration in Brg1-deficient retinae. Despite the hypocellularity, premature cell cycle exit, increased cell death, and extended cell cycle length, retinal progenitor cells persisted in Brg1-deficient retinae, thereby making them more susceptible to retinoblastoma. ChIP-seq analysis provided insight into the underlying molecular mechanisms of these complex Brg1-regulated cellular processes during retinal development.

Publication Title

Brg1 coordinates multiple processes during retinogenesis and is a tumor suppressor in retinoblastoma.

Sample Metadata Fields

Specimen part

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accession-icon GSE66721
Suppression of virus-induced CCL2, CXCL10 and IL-6: biomarkers of Lactobacillus-mediated protection at the respiratory tract
  • organism-icon Mus musculus
  • sample-icon 22 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

In this manuscript, we present a more extensive analysis of inflammatory suppression mediated by L. plantarum at the respiratory tract. Via full genome microarray of whole lung tissue, we have generated an extensive list of soluble proinflammatory mediators that are expressed in response to PVM infection and we identify those mediators that are suppressed and also those that are not suppressed in response to L. plantarum priming. We focused further study on three specific virus-induced soluble mediators that are differentially expressed and that serve as specific biomarkers for Lactobacillus-mediated survival in response to acute respiratory virus infection. Among several novel directions, we use these biomarker cytokines to explore Lactobacillus-mediated actions at the respiratory tract that are unique and distinct from those taking place at gastrointestinal mucosa.

Publication Title

Immunobiotic Lactobacillus administered post-exposure averts the lethal sequelae of respiratory virus infection.

Sample Metadata Fields

Specimen part

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accession-icon GSE45987
A transcriptomic analysis of a Caucasian family cohort of high risks for the metabolic syndrome
  • organism-icon Homo sapiens
  • sample-icon 298 Downloadable Samples
  • Technology Badge IconIllumina HumanWG-6 v3.0 expression beadchip

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

A comprehensive analysis of adiponectin QTLs using SNP association, SNP cis-effects on peripheral blood gene expression and gene expression correlation identified novel metabolic syndrome (MetS) genes with potential role in carcinogenesis and systemic inflammation.

Sample Metadata Fields

Sex, Age, Race

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accession-icon SRP052612
Loss of endometrial plasticity in recurrent pregnancy loss (RNA-Seq)
  • organism-icon Homo sapiens
  • sample-icon 20 Downloadable Samples
  • Technology Badge IconIlluminaHiSeq2000

Description

In order to try and identify characteristics of gene expression in the endometrium of women suffering infertility or recurrenty miscarriage, we performed RNAseq on endometrial pipelle biopsies from 20 women. The endometrial transcriptome in the mid-luteal phase of the cycle (window of implantation) is highly divergent in women suffering infertility or miscarriages. Overall design: 20 mid-luteal endometrial biopsies were analysed from infertile women and patients suffering recurrent pregnancy loss. 

Publication Title

Loss of Endometrial Plasticity in Recurrent Pregnancy Loss.

Sample Metadata Fields

No sample metadata fields

View Samples
accession-icon GSE27516
Preclinical Models for Neuroblastoma: Establishing a Baseline for Treatment
  • organism-icon Mus musculus
  • sample-icon 17 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

Here we characterize and optimize both systems to increase their utility for preclinical studies. We show that TH-MYCN mice develop tumors in the paraspinal ganglia, but not in the adrenal, with cellular and gene expression patterns similar to human NB. In addition, we present a new ultrasound guided, non-invasive orthotopic xenograft method. This injection technique is rapid, provides accurate targeting of the injected cells and leads to efficient engraftment. We also demonstrate that tumors can be detected, monitored and quantified prior to visualization using ultrasound, MRI and bioluminescence. Finally we develop and test a standard of care chemotherapy regimen. This protocol, which is based on current treatments for neuroblastoma, provides a baseline for comparison of new therapeutic agents.

Publication Title

Preclinical models for neuroblastoma: establishing a baseline for treatment.

Sample Metadata Fields

Specimen part

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accession-icon SRP094125
Integration of kinase and calcium signaling at the level of chromatin underlines inducible gene activation in T cells
  • organism-icon Homo sapiens
  • sample-icon 15 Downloadable Samples
  • Technology Badge Icon

Description

Aim: to perform a genome-wide investigation of chromatin landscape and gene expression patterns downstream of calcium and kinase signaling in Jurkat T cells. Methods: PMA and ionomycin were used to activate the calcium and kinase signalling networks involved in T cell activation. Global gene expression was measured using RNA-seq, whilst ATAC-seq was used to probe chromatin landscape following 3 hours of stimulation with PMA, ionomycin or both. All experiments were performed in triplicate. For RNA-seq all sequencing was performed using paired-end sequencing on an Illumina HiSeq2500 instrument. For ATAC-seq sequencing was performed using a HiSeq 1500. Results: we mapped approximately 60 million reads per sample for ATAC-seq, and 22 million reads per library for RNA-seq. Overall we identified 57,825 transcripts and 19,763 ATAC-seq peaks. We identifiead 1648 genes whose expression was increased by 2-fold or more by at least one treatment in comparison to untreated cells. Similarly, we identified 3972 ATAC peaks that were induced by at least 2-fold by treatment in comparison to untreated cells. Conclusions: we found that chromatin landscape was associated with gene expression downstream of calcium and kinase signaling in Jurkat cells. Further to this we found that activation of the full complement of TCR-responsive genes is dependent upon both PMA and ionomycin, and amounts to more than just the sum of both. Overall design: RNA-sequencing and ATAC-sequencing were performed after 3 hours of treatment with either PMA, ionomycin or co-treatment with PMA and ionomycin.

Publication Title

Integration of Kinase and Calcium Signaling at the Level of Chromatin Underlies Inducible Gene Activation in T Cells.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE29686
Coexpression of Normally Incompatible Developmental Pathways in Retinoblastoma Genesis
  • organism-icon Mus musculus, Homo sapiens
  • sample-icon 211 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

Coexpression of normally incompatible developmental pathways in retinoblastoma genesis.

Sample Metadata Fields

Specimen part

View Samples
accession-icon GSE29685
Coexpression of Normally Incompatible Developmental Pathways in Retinoblastoma Genesis [mouse model data]
  • organism-icon Mus musculus
  • sample-icon 132 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

It is widely believed that the molecular and cellular features of a tumor reflect its cell-of-origin and can thus provide clues about treatment targets. The retinoblastoma cell-of-origin has been debated for over a century. Here we report that human and mouse retinoblastomas have molecular, cellular, and neurochemical features of multiple cell classes, principally amacrine/horizontal interneurons, retinal progenitor cells, and photoreceptors. Importantly, single-cell gene expression array analysis showed that these multiple cell typespecific developmental programs are coexpressed in individual retinoblastoma cells, which creates a progenitor/neuronal hybrid cell. Importantly, neurotransmitter receptors, transporters, and biosynthetic enzymes are expressed in human retinoblastoma, and targeted disruption of these pathways reduces retinoblastoma growth in vivo and in vitro. Our finding that retinoblastoma tumor cells express multiple neuronal differentiation programs that are normally incompatible in development suggests that the pathways that control retinal development and establish distinct cell types are perturbed during tumorigenesis. Therefore, the cell-of-origin for retinoblastoma cannot be inferred from the features of the tumor cells themselves. However, we now have a detailed understanding of the neuronal pathways that are deregulated in retinoblastoma and targeting the catecholamine and indolamine receptors or downstream components could provide useful therapeutic approaches in future studies. This example highlights the importance of comprehensive molecular, cellular and physiological characterization of human cancers with single cell resolution as we incorporate molecular targeted therapy into treatment regimens.

Publication Title

Coexpression of normally incompatible developmental pathways in retinoblastoma genesis.

Sample Metadata Fields

No sample metadata fields

View Samples
accession-icon GSE29683
Coexpression of Normally Incompatible Developmental Pathways in Retinoblastoma Genesis [human tumor/cell line data]
  • organism-icon Homo sapiens
  • sample-icon 59 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

It is widely believed that the molecular and cellular features of a tumor reflect its cell-of-origin and can thus provide clues about treatment targets. The retinoblastoma cell-of-origin has been debated for over a century. Here we report that human and mouse retinoblastomas have molecular, cellular, and neurochemical features of multiple cell classes, principally amacrine/horizontal interneurons, retinal progenitor cells, and photoreceptors. Importantly, single-cell gene expression array analysis showed that these multiple cell typespecific developmental programs are coexpressed in individual retinoblastoma cells, which creates a progenitor/neuronal hybrid cell. Importantly, neurotransmitter receptors, transporters, and biosynthetic enzymes are expressed in human retinoblastoma, and targeted disruption of these pathways reduces retinoblastoma growth in vivo and in vitro. Our finding that retinoblastoma tumor cells express multiple neuronal differentiation programs that are normally incompatible in development suggests that the pathways that control retinal development and establish distinct cell types are perturbed during tumorigenesis. Therefore, the cell-of-origin for retinoblastoma cannot be inferred from the features of the tumor cells themselves. However, we now have a detailed understanding of the neuronal pathways that are deregulated in retinoblastoma and targeting the catecholamine and indolamine receptors or downstream components could provide useful therapeutic approaches in future studies. This example highlights the importance of comprehensive molecular, cellular and physiological characterization of human cancers with single cell resolution as we incorporate molecular targeted therapy into treatment regimens.

Publication Title

Coexpression of normally incompatible developmental pathways in retinoblastoma genesis.

Sample Metadata Fields

Specimen part

View Samples
accession-icon GSE29684
Coexpression of Normally Incompatible Developmental Pathways in Retinoblastoma Genesis [single tumor cell data]
  • organism-icon Homo sapiens
  • sample-icon 20 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

It is widely believed that the molecular and cellular features of a tumor reflect its cell-of-origin and can thus provide clues about treatment targets. The retinoblastoma cell-of-origin has been debated for over a century. Here we report that human and mouse retinoblastomas have molecular, cellular, and neurochemical features of multiple cell classes, principally amacrine/horizontal interneurons, retinal progenitor cells, and photoreceptors. Importantly, single-cell gene expression array analysis showed that these multiple cell typespecific developmental programs are coexpressed in individual retinoblastoma cells, which creates a progenitor/neuronal hybrid cell. Importantly, neurotransmitter receptors, transporters, and biosynthetic enzymes are expressed in human retinoblastoma, and targeted disruption of these pathways reduces retinoblastoma growth in vivo and in vitro. Our finding that retinoblastoma tumor cells express multiple neuronal differentiation programs that are normally incompatible in development suggests that the pathways that control retinal development and establish distinct cell types are perturbed during tumorigenesis. Therefore, the cell-of-origin for retinoblastoma cannot be inferred from the features of the tumor cells themselves. However, we now have a detailed understanding of the neuronal pathways that are deregulated in retinoblastoma and targeting the catecholamine and indolamine receptors or downstream components could provide useful therapeutic approaches in future studies. This example highlights the importance of comprehensive molecular, cellular and physiological characterization of human cancers with single cell resolution as we incorporate molecular targeted therapy into treatment regimens.

Publication Title

Coexpression of normally incompatible developmental pathways in retinoblastoma genesis.

Sample Metadata Fields

Specimen part

View Samples

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)

fund-icon Fund the CCDL

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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