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accession-icon SRP052034
Conversion of Human Fibroblasts to Stably Self-Renewing Neural Stem Cells with a Single Zinc-Finger Transcription Factor
  • organism-icon Homo sapiens
  • sample-icon 9 Downloadable Samples
  • Technology Badge IconIlluminaHiSeq1500

Description

Direct conversion of somatic cells into neural stem cells (NSCs) by defined factors holds great promise for mechanistic studies, drug screening, and potential cell therapies for different neurodegenerative diseases. Here, we report that a single zinc-finger transcription factor, Zfp521, is sufficient for direct conversion of human fibroblasts into long-term self-renewable and multipotent NSCs. In vitro, Zfp521-induced NSCs maintained their characteristics in the absence of exogenous factor expression and exhibited morphological, molecular, developmental, and functional properties that were similar to control NSCs. Additionally, the single seeded induced NSCs were able to form NSC colonies with efficiency comparable to control NSCs and expressed NSC markers. The converted cells were capable of surviving, migrating and attaining neural phenotypes after transplantation into neonatal mouse- and adult rat brains, without forming tumors. Moreover, the Zfp521-induced NSCs predominantly expressed rostral genes. Our results suggest a facilitated approach for establishing human NSCs through Zfp521-driven conversion of fibroblasts. Overall design: RNA-Seq of 3 replicates each of iNSC, WT-NSC, and HNF

Publication Title

Conversion of Human Fibroblasts to Stably Self-Renewing Neural Stem Cells with a Single Zinc-Finger Transcription Factor.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE75700
Differential gene expression in the liver among crossbred beef steers with divergent gain and feed intake phenotypes
  • organism-icon Bos taurus
  • sample-icon 16 Downloadable Samples
  • Technology Badge Icon Bovine Gene 1.1 ST Array (bovgene11st)

Description

Steer liver transcriptome

Publication Title

Differential expression of genes related to gain and intake in the liver of beef cattle.

Sample Metadata Fields

Sex, Specimen part

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accession-icon GSE29402
Comparative gene expression in the human conjunctiva and cornea
  • organism-icon Homo sapiens
  • sample-icon 4 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

The identification of a marker that is expressed in the conjunctival epithelium but not in the corneal epithelium has been a growing need. A more specific marker of limbal and conjunctival epithelia would be necessary to detect non-corneal epithelial cells on the corneal surface. To search for conjunctival specific marker(s), we first performed preferential gene profiling in the conjunctiva in direct comparison to that in the cornea using microarray technique.

Publication Title

Keratin 13 is a more specific marker of conjunctival epithelium than keratin 19.

Sample Metadata Fields

Specimen part

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accession-icon GSE19156
Air-liquid interfacial biofilm vs planktonic S. cerevisiae cells
  • organism-icon Saccharomyces cerevisiae
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Yeast Genome S98 Array (ygs98)

Description

Goal was to identify yeast genes whose expression changed as a function of the shift from growth in bulk culture to growth in an air-liquid interfacial biofilm.

Publication Title

Ethanol-independent biofilm formation by a flor wine yeast strain of Saccharomyces cerevisiae.

Sample Metadata Fields

Specimen part

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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 GSE20559
Gene expression signature reflects differentiation differences rather than telomere maintenance mechanism
  • organism-icon Homo sapiens
  • sample-icon 37 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

A gene expression signature purporting to distinguish between telomerase and ALT immortalization has recently been described (Lafferty-Whyte et al., 2009). This was obtained as the intersection of two independent signatures, one obtained from cell lines and the other from a panel of liposarcomas, which utilize different telomere maintenance mechanisms (TMMs). To assess the utility of this signature we used Affymetrix U133plus2.0 arrays to undertake a similar analysis of an independent collection of liposarcomas of defined TMM. In our dataset, the 297 gene signature causes the liposarcomas to cluster not on the basis of TMM, but rather on the basis of tumor histological subtype [Figure 1], consistent with the signatures reported by others (Matushansky et al., 2008).

Publication Title

Validating a gene expression signature proposed to differentiate liposarcomas that use different telomere maintenance mechanisms.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE31562
Rapid and robust generation of functional oligodendrocyte progenitor cells from epiblast stem cells
  • organism-icon Mus musculus
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

Stem cell biology has garnered much attention due to its potential to impact human health through disease modeling and cell replacement therapy. This is especially pertinent to myelin-related disorders such as multiple sclerosis and leukodystrophies where restoration of normal oligodendrocyte function could provide an effective treatment. Progress in myelin repair has been constrained by the difficulty in generating pure populations of oligodendrocyte progenitor cells (OPCs) in sufficient quantities. Pluripotent stem cells theoretically provide an unlimited source of OPCs but significant advances are currently hindered by heterogeneous differentiation strategies that lack reproducibility. Here we provide a platform for the directed differentiation of pluripotent mouse epiblast stem cells (EpiSCs) through a defined series of developmental transitions into a pure population of highly expandable OPCs in ten days. These OPCs robustly differentiate into myelinating oligodendrocytes both in vitro and in vivo. Our results demonstrate that pluripotent stem cells can provide a pure population of clinically-relevant, myelinogenic oligodendrocytes and offer a tractable platform for defining the molecular regulation of oligodendrocyte development, drug screening, and potential cell-based remyelinating therapies.

Publication Title

Rapid and robust generation of functional oligodendrocyte progenitor cells from epiblast stem cells.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE27855
Genome wide expression analysis of EST-induced EBE-XVE using Affymetrix ATH1 array
  • organism-icon Arabidopsis thaliana
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)

Description

Global transcriptome patterns were determined in XVE-14 and wild-type seedlings induced for 45 min b-estradiol in order to identify the genes early regulated by EBE transcription factor.

Publication Title

EBE, an AP2/ERF transcription factor highly expressed in proliferating cells, affects shoot architecture in Arabidopsis.

Sample Metadata Fields

Specimen part

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accession-icon GSE49800
Effects of CPAP Therapy on Leukocyte Gene Expression
  • organism-icon Homo sapiens
  • sample-icon 36 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Gene 1.0 ST Array (hugene10st)

Description

Rationale: Obstructive sleep apnea (OSA) has been associated with a number of chronic disorders that may improve with effective therapy. However, the molecular pathways affected by continuous positive airway pressure (CPAP) treatment are largely unknown. We sought to assess the system-wide consequences of CPAP therapy by transcriptionally profiling peripheral blood leukocytes (PBLs). Methods: Subjects diagnosed with severe OSA were treated with CPAP, and whole-genome expression measurement of PBLs was performed at baseline and following therapy. We used Gene Set Enrichment Analysis (GSEA) to identify gene sets that were differentially enriched. Network analysis was then applied to identify key drivers of pathways influenced by CPAP. Results: 18 subjects with severe OSA (apnea hypopnea index 30 events/hour) underwent CPAP therapy and microarray analysis of their PBLs. Treatment with CPAP improved AHI, daytime sleepiness and blood pressure but did not affect anthropometric measures. GSEA revealed a number of enriched gene sets, many of which were involved in neoplastic processes and displayed down-regulated expression patterns in response to CPAP. Network analysis identified several densely connected genes that are important modulators of cancer and tumor growth. Conclusions: Effective therapy of OSA with CPAP is associated with alterations in circulating leukocyte gene expression. Functional enrichment and network analyses highlighted transcriptional suppression in cancer-related pathways suggesting potentially novel mechanisms linking OSA with neoplastic signatures.

Publication Title

Treatment of obstructive sleep apnea alters cancer-associated transcriptional signatures in circulating leukocytes.

Sample Metadata Fields

Treatment, Subject

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accession-icon GSE45440
Transcription factormediated reprogramming of fibroblasts to expandable, myelinogenic oligodendrocyte progenitor cells
  • organism-icon Mus musculus
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

Cell-based therapies for myelin disorders, such as multiple sclerosis and leukodystrophies, require technologies to generate functional oligodendrocyte progenitor cells. Here we describe direct conversion of mouse embryonic and lung fibroblasts to induced oligodendrocyte progenitor cells (iOPCs) using sets of either eight or three defined transcription factors. iOPCs exhibit a bipolar morphologyical and global gene expression profile molecular features consistent with bona fide OPCs. They can be expanded in vitro for at least five passages while retaining the ability to differentiate into induced multiprocessed oligodendrocytes. When transplanted to hypomyelinated mice, iOPCs are capable of ensheathing host axons and generating compact myelinmyelinating axons both in vitro and in vivo. Lineage conversion of somatic cells to expandable iOPCs provides a strategy to study the molecular control of oligodendrocyte lineage identity and may facilitate neurological disease modeling and autologous remyelinating therapies.

Publication Title

Transcription factor-mediated reprogramming of fibroblasts to expandable, myelinogenic oligodendrocyte progenitor cells.

Sample Metadata Fields

Specimen part, Treatment

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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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