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accession-icon GSE35603
Network Biology of Tumor Stem-like Cells Identified a Regulatory Role of CBX5 in Lung Cancer
  • organism-icon Homo sapiens
  • sample-icon 74 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Mounting evidence points to a link between a cancer possessing stem-like properties and a worse prognosis. To understand the biology, a common approach is to integrate network biology with signal processing mechanics. That said, even with the right tools, predicting the risk for a highly susceptible target using only a handful of gene signatures remains very difficult. By compiling the expression profiles of a panel of tumor stem-like cells (TSLCs) originating in different tissues, comparing these to their parental tumor cells (PTCs) and the human embryonic stem cells (hESCs), and integrating network analysis with signaling mechanics, we propose that network topologically-weighted signaling processing measurements under tissue-specific conditions can provide scalable and predicable target identification.

Publication Title

Network biology of tumor stem-like cells identified a regulatory role of CBX5 in lung cancer.

Sample Metadata Fields

Specimen part

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accession-icon GSE96853
Characterization of transcriptomes of human iPSC-derived retinal lineages
  • organism-icon Homo sapiens
  • sample-icon 8 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Retinal ganglion cells (RGCs) and retinal pigment epithelium (RPE) cells are two retinal cell types that are affected by the most prevalent retinal diseases leading to irreversible blindness, such as glaucoma affecting the former and age-related macular degeneration affecting the latter. One of the most promising approaches for the therapy of these diseases is via the autologous transplantation of RGC or RPE cells derived from the induced pluripotent stem cells (iPSCs). This emphasizes the importance of detailed characterization and understanding of the mechanisms of differentiation of iPSCs into retinal lineages on the genome-wide scale. Such information can be used to identify novel crucial regulators of differentiation, optimisation of differentiation protocols to make them more efficient and safe, identification of novel specific biomarker signatures of differentiated cells. In this study, we performed the genome-wide transcriptome analysis of terminally differentiated RGC and RPE lineages, as well as intermediate retinal progenitor cells (RPCs) of optic vesicles (OVs) derived from the human induced pluripotent stem cells (iPSCs). In our analysis we specifically focused on the classes of transcripts that encode regulators of gene expression, such as transcription factors, epigenetic factors, and components of signaling pathways.

Publication Title

Expression profiling of cell-intrinsic regulators in the process of differentiation of human iPSCs into retinal lineages.

Sample Metadata Fields

Specimen part

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accession-icon GSE13727
PBMS cells from SJS/TEN
  • organism-icon Homo sapiens
  • sample-icon 5 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis

Publication Title

Granulysin is a key mediator for disseminated keratinocyte death in Stevens-Johnson syndrome and toxic epidermal necrolysis.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE13726
SJS blister cells
  • organism-icon Homo sapiens
  • sample-icon 5 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis

Publication Title

Granulysin is a key mediator for disseminated keratinocyte death in Stevens-Johnson syndrome and toxic epidermal necrolysis.

Sample Metadata Fields

No sample metadata fields

View Samples
accession-icon GSE13229
Comparison of mouse NK cell subsets defined by CD27 and CD11b expression
  • organism-icon Mus musculus
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

Previous reports have defined three subsets of mouse NK cells on the basis of the expression of CD27 and CD11b. The developmental relationship between these subsets was unclear. To address this issue, we evaluated the overall proximity between mouse NK cell subsets defined by CD27 and CD11b expression using pangenomic gene expression profiling. The results suggest that CD27+CD11b-, CD27+CD11b+ and CD27-CD11b+ correspond to three different intermediates stages of NK cell development.

Publication Title

Maturation of mouse NK cells is a 4-stage developmental program.

Sample Metadata Fields

No sample metadata fields

View Samples
accession-icon GSE14773
Roles of EMT regulator in colon cancer
  • organism-icon Homo sapiens
  • sample-icon 8 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Isolation and enrichment of cancer stem cells in colorectal carcinoma to study role of epithelial-mesenchymal transition regilators in tumor malignancy.

Publication Title

SNAIL regulates interleukin-8 expression, stem cell-like activity, and tumorigenicity of human colorectal carcinoma cells.

Sample Metadata Fields

Cell line

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accession-icon GSE19449
Doxorubicin resistance in a novel in vitro model of human pleomorphic liposarcoma associated with ALT
  • organism-icon Homo sapiens
  • sample-icon 35 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Soft tissue sarcomas are a diverse set of fatal human tumors where few agents have demonstrable clinical efficacy, with the standard therapeutic combination of doxorubicin and ifosfamide showing only a 25-30% response rate in large multi-institutional trials. Although liposarcomas are the most common histological form of adult soft tissue sarcomas, research in this area is severely hampered by the lack of experimentally tractable in vitro model systems. To this end, here we describe a novel in vitro model for human pleomorphic liposarcoma. The cell line (LS2) is derived from a pleomorphic liposarcoma that utilizes Alternative Lengthening of Telomeres (ALT) mechanism of telomere maintenance, which may be particularly important in modulating the response of this tumor type to DNA damaging agents. We present detailed baseline molecular and genomic data, including genome wide copy number and transcriptome profiles, for this model compared to its parental tumor and a panel of liposarcomas covering multiple histologies. The model has retained essentially all of the detectable alterations in copy number that are seen in the parental tumor, and shows molecular karyotypic and expression profiles consistent with pleomorphic liposarcomas. We also demonstrate the utility of this model, together with two additional human liposarcoma cell lines, to investigate the relationship between topoisomerase 2A expression and the sensitivity of ALT-positive liposarcomas to doxorubicin. This model, together with its associated baseline data, provide a powerful new tool to develop treatments for this clinically poorly-tractable tumor, and to investigate the contribution that ALT makes to modulating sensitivity to DNA damaging chemotherapeutic agents such as doxorubicin.

Publication Title

Doxorubicin resistance in a novel in vitro model of human pleomorphic liposarcoma associated with alternative lengthening of telomeres.

Sample Metadata Fields

Cell line

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accession-icon GSE27280
Pompe disease induced pluripotent stem cells for pathogenesis modeling, drug testing and disease marker identification
  • organism-icon Homo sapiens
  • sample-icon 10 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Pompe disease is caused by autosomal recessive mutations in the GAA gene, which encodes acid alpha-glucosidase. Although enzyme replacement therapy has recently improved patient survival greatly, the results in skeletal muscles and for advanced disease are still not satisfactory. Here, we report the derivation of Pompe disease induced pluripotent stem cells (PomD-iPSCs) and their potential for pathogenesis modeling, drug testing and disease marker identification. PomD-iPSCs maintained pluripotent features, and had low GAA activity and high glycogen content. Cardiomyocyte-like cells (CMLCs) differentiated from PomD-iPSCs recapitulated the hallmark Pompe disease pathophysiological phenotypes, including high levels of glycogen, abundant intracellular LAMP-1- or LC3-positive granules, and multiple ultrastructural aberrances. Drug rescue assessment showed that exposure of PomD-iPSC-derived CMLCs to rhGAA reversed the major pathologic phenotypes. Further, L-carnitine and 3- methyladenine treatment reduced defective cellular respiration and buildup of phagolysosomes, respectively, in the diseased cells. By comparative transcriptome analysis, we identified glycogen metabolism, lysosome and mitochondria related marker genes whose expression robustly correlated with the therapeutic effect of drug treatment in PomD-iPSC-derived CMLCs. Collectively, these results demonstrate that PomD-iPSCs are a promising in vitro disease model for development of novel therapeutic strategies for Pompe disease.

Publication Title

Human Pompe disease-induced pluripotent stem cells for pathogenesis modeling, drug testing and disease marker identification.

Sample Metadata Fields

Specimen part

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accession-icon GSE103619
Gene expression profiles of hiPSC-derived retinal ganglion cells in MT-ND4 mutated Leber's hereditary optic neuropathy
  • organism-icon Homo sapiens
  • sample-icon 3 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Lebers hereditary optic neuropathy (LHON) is a maternally inherited mitochondrial disease caused by homoplasmic mutations in complex I subunit genes, and is characterized by incomplete penetrance. The mechanism of low penetrance of complex I mutation is still largely unclear today. In this study, we created the patient-specific induced pluripotent stem cells (iPSCs) from MT-ND4 mutated LHON affected patient, asymptomatic mutation carrier and control, and differentiated them into retinal ganglion cells (RGCs) for pathogenesis survey. We observed the following phenotypic features in the LHON-specific RGCs as compared to the control: 1) enhanced mitochondrial biogenesis in affected and carriers; 2) compensatory increased mitochondrial complex I activity in carrier, but not in affected patient; 3) reduced spare respiratory activity in affected and carrier. Microarray profiling of LHON-specific RGCs revealed abundant overexpression of genes encoding components of cell cycle regulation machinery as compared to the control.

Publication Title

Bioactivity and gene expression profiles of hiPSC-generated retinal ganglion cells in MT-ND4 mutated Leber's hereditary optic neuropathy.

Sample Metadata Fields

Specimen part, Disease

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accession-icon SRP068735
MicroRNAs 24 and 27 suppress allergic inflammation and target a network of regulators of T helper-2 cell-associated cytokine production
  • organism-icon Mus musculus
  • sample-icon 16 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2500

Description

MicroRNAs (miRNAs) are important regulators of cell fate decisions in immune responses. They act by coordinate repression of multiple target genes, a property that we exploited to uncover regulatory networks that govern T helper-2 (Th2) cells. A functional screen of individual miRNAs in primary T cells uncovered multiple miRNAs that inhibited Th2 cell differentiation. Among these were miR-24 and miR-27, miRNAs coexpressed from two genomic clusters, which each functioned independently to limit interleukin-4 (IL-4) production. Mice lacking both clusters in T cells displayed increased Th2 cell responses and tissue pathology in a mouse model of asthma. Gene expression and pathway analyses placed miR-27 upstream of genes known to regulate Th2 cells. They also identified targets not previously associated with Th2 cell biology which regulated IL-4 production in unbiased functional testing. Thus, elucidating the biological function and target repertoire of miR-24 and miR-27 reveals regulators of Th2 cell biology. Overall design: Gene expression analysis of miRNA-deficient mouse CD4+ T cells transfected with miRNA mimics twice over a 5 day in vitro culture in the presence of low amounts of exogenous IL-4 (10U/ml). Cells transfected with either miR-23, miR-24 or miR-27 were compared to cells transfected with a control mimic. Data are from at least biologic triplicates.

Publication Title

MicroRNAs 24 and 27 Suppress Allergic Inflammation and Target a Network of Regulators of T Helper 2 Cell-Associated Cytokine Production.

Sample Metadata Fields

Cell line, Subject

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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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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