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accession-icon GSE42600
Gene expression profiling in cells with Ago1 knockdown (Affymetrix)
  • organism-icon Homo sapiens
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Gene 1.0 ST Array (hugene10st)

Description

Argonautes, a family of highly evolutionarily conserved proteins, are the central platform for small RNA-mediated gene regulatory mechanisms which occur mainly in the cytoplasm. To understand a potential role of Argonaute 1 (Ago1) protein in the nucleus of mammalian cells in regulating gene transcription and epigenetics, we performed integrated analyses of Ago1 ChIP-sequencing (GSE40536) and gene expression profiling in cells depleted of Ago1. For gene expression profiling, we knocked down the expression of Ago1 by siRNA in PC-3 cells and compared gene expression profiles in the cells depleted of Ago1 and cells receiving control treatments. We found that Ago1 depletion resulted in more downregulated genes which were enriched in gene responsible for promoting cell cycle progression, DNA replication and repair, and response to endogenous stimuli. Integrated analyses of Ago1-chromosomal interactions and gene expression changes in response to Ago1 depletion reveal a significant correlation between Ago1-bound genes and genes altered by Ago1 depletion. These genes are significantly enriched in cancer-related pathways. Our data suggests a nuclear function of Ago1 in regulating gene transcription.

Publication Title

Ago1 Interacts with RNA polymerase II and binds to the promoters of actively transcribed genes in human cancer cells.

Sample Metadata Fields

Cell line, Treatment

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accession-icon GSE110452
IRF8 regulates transcription of Naips for NLRC4 inflammasome activation
  • organism-icon Mus musculus
  • sample-icon 4 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 2.0 ST Array (mogene20st)

Description

Inflammasome activation is critical for host defense against various microbial infections. Activation of the NLRC4 inflammasome requires detection of flagellin or type III secretion system (T3SS) components by NLR family apoptosis inhibitory proteins (NAIPs); yet how this pathway is regulated is unknown. Here we found that interferon regulatory factor 8 (IRF8) is required for optimal activation of the NLRC4 inflammasome in bone marrow-derived macrophages infected with Salmonella Typhimurium, Burkholderia thailandensis, or Pseudomonas aeruginosa but is dispensable for activation of the canonical and non-canonical NLRP3, AIM2, and Pyrin inflammasomes. IRF8 governs the transcription of Naips to allow detection of flagellin or T3SS proteins to mediate NLRC4 inflammasome activation. Furthermore, we found that IRF8 confers protection against bacterial infection in vivo, owing to its role in inflammasome-dependent cytokine production and pyroptosis. Altogether, our findings suggest that IRF8 is a critical regulator of NAIPs and NLRC4 inflammasome activation for defense against bacterial infection.

Publication Title

IRF8 Regulates Transcription of Naips for NLRC4 Inflammasome Activation.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE42986
Transcriptome profiling in human primary mitochondrial respiratory chain disease
  • organism-icon Homo sapiens
  • sample-icon 53 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Exon 1.0 ST Array [CDF: CHOP_1.0_ENTREZG (huex10st)

Description

Primary mitochondrial respiratory chain (RC) diseases are heterogeneous in etiology and manifestations but collectively impair cellular energy metabolism. To identify a common cellular response to RC disease, systems biology level transcriptome investigations were performed in human RC disease skeletal muscle and fibroblasts. Global transcriptional and post-transcriptional dysregulation in a tissue-specific fashion was identified across diverse RC complex and genetic etiologies. RC disease muscle was characterized by decreased transcription of cytosolic ribosomal proteins to reduce energy-intensive anabolic processes, increased transcription of mitochondrial ribosomal proteins, shortened 5'-UTRs to improve translational efficiency, and stabilization of 3'-UTRs containing AU-rich elements. These same modifications in a reversed direction typified RC disease fibroblasts. RC disease also dysregulated transcriptional networks related to basic nutrient-sensing signaling pathways, which collectively mediate many aspects of tissue-specific cellular responses to primary RC disease. These findings support the utility of a systems biology approach to improve mechanistic understanding of mitochondrial RC disease.

Publication Title

Primary respiratory chain disease causes tissue-specific dysregulation of the global transcriptome and nutrient-sensing signaling network.

Sample Metadata Fields

Sex, Age, Specimen part

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accession-icon GSE15141
EGR1 regulates metastatic potential of v-src transformed chicken sarcoma cell lines
  • organism-icon Gallus gallus
  • sample-icon 9 Downloadable Samples
  • Technology Badge Icon Affymetrix Chicken Genome Array (chicken)

Description

A model of tumor metastasis based on v-src transformed immortalized cell lines was developed. The model consists of highly metastatic PR9692 cell line and a derived clone PR9692-E9 which has lost the metastatic abilities. Introduction of exogenous EGR1 gene into the non-metastasizing PR9692-E9 cells completely restores the metastatic potential. Revealed changes in gene expression provide insight into the molecular mechanisms contolling metastatic behavior of sarcoma cells.

Publication Title

The transcription factor EGR1 regulates metastatic potential of v-src transformed sarcoma cells.

Sample Metadata Fields

Cell line

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accession-icon GSE42516
Downregulation of the HOPX gene decreases metastatic activity in a chicken sarcoma cell line model and identifies genes associated with metastasis
  • organism-icon Gallus gallus
  • sample-icon 4 Downloadable Samples
  • Technology Badge Icon Affymetrix Chicken Genome Array (chicken)

Description

Metastatic progression is the leading cause of cancer mortality yet we have an incomplete view of the genetic events governing this process. An investigation was undertaken to explore the role of homeodemain only protein X (HOPX) in metastatic propensity and to identify other genes that may participate in metastasis development. The transcription factor HOPX was assessed for its possible involvement in metastasis formation using a knock-down induced by plasmid-delivered shRNAs. We used our original model system of chicken v-src-transformed tumour cell line PR9692 and its subclone (PR9692-E9) that have lost the ability to induce metastases after inoculation into syngeneic chickens without any significant change in primary tumour formation. We found that also a PR9692 cell line with decreased expression of HOPX gene (PR9692-shHOPX) lost its metastatic capacity in vivo (in chickens) and displayed a reduced cell migration in vitro. We compared the gene expression profiles of control (PR9692-shMOCK) and PR9692-shHOPX cells using oligonucleotide microarrays, assuming that genes with differential expression might be associated with metastasis. The data were compared with a previous study showing differences in gene expression between the PR9692 and PR9692-E9 cells. Bioinformatics was applied to identify gene expression patterns associated with metastasis. 234 genes were identified to show at least 2-fold change in both pairs of cell lines. The results were validated with real-time quantitative RT-PCR and the differential expression was confirmed for several genes. We were also able to demonstrate a significant change at protein level in case of three selected genes (NCAM, FOXG1, ITGA4). shRNA mediated knockdown of one of the identified HOPX regulated genes (integrin alpha 4) in the PR9692 cell line itself showed a marked inhibition of metastasis formation.

Publication Title

Downregulation of HOPX controls metastatic behavior in sarcoma cells and identifies genes associated with metastasis.

Sample Metadata Fields

Cell line

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accession-icon GSE11302
Gene expression analysis upon exposure of hESCs to novel set of self-renewal and differentiation compounds
  • organism-icon Homo sapiens
  • sample-icon 34 Downloadable Samples
  • Technology Badge IconIllumina humanRef-8 v2.0 expression beadchip

Description

Here we present a strategy to adapt hESCs to high-throughput screening (HTS) conditions, resulting in an assay suitable for the discovery of small molecules that drive hESC self-renewal or differentiation. Use of this new assay has led to the identification of several currently marketed drugs and natural compounds promoting short-term hESC maintenance and compounds directing early lineage choice. Global gene expression analysis upon drug treatment reveals overlapping and novel pathways correlated to hESC self-renewal and differentiation. Our results demonstrate feasibility of hESC-based HTS and enhance the available repertoire of chemical compounds for manipulating hESC fate.

Publication Title

High-throughput screening assay for the identification of compounds regulating self-renewal and differentiation in human embryonic stem cells.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE42214
Wheat drought responses
  • organism-icon Triticum aestivum
  • sample-icon 12 Downloadable Samples
  • Technology Badge Icon Affymetrix Wheat Genome Array (wheat)

Description

Three wheat genotypes were exposed to water stress and root tissue collected for expression analysis

Publication Title

Introgression of novel traits from a wild wheat relative improves drought adaptation in wheat.

Sample Metadata Fields

Specimen part

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accession-icon GSE64965
Expression profile of osteosarcoma cells in which Sox2 maintains cancer stem cells
  • organism-icon Mus musculus
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)

Description

Sox2 is required to maintain osteosarcoma cell tumor initiation.Knockdown of Sox2 leads tpo loss of tumorigenic properties. To examine gene expression changes upon Sox2 knockdown, we performed microarray analysis on mouse osteosarcoma cells expressing scrambled or Sox2shRNA. We found that genes upregulated upon Sox2 knockdown included osteoblast diffrentiation genes and genes down regulated included cell cycle and RNA processing genes as well as YAP-TEAD target genes.

Publication Title

Sox2 antagonizes the Hippo pathway to maintain stemness in cancer cells.

Sample Metadata Fields

Specimen part, Cell line

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accession-icon SRP065767
Recruitment of Rod Photoreceptors from Short Wavelength Sensitive Cones during the Evolution of Nocturnal Vision in Mammals
  • organism-icon Mus musculus
  • sample-icon 30 Downloadable Samples
  • Technology Badge IconIllumina Genome Analyzer IIx

Description

Vertebrate ancestors had only cone-like photoreceptors. The duplex retina evolved in jawless vertebrates with the advent of highly photosensitive rod-like photoreceptors. Despite cones being the arbiters of high-resolution color vision, rods emerged as the dominant photoreceptor in mammals during a nocturnal phase early in their evolution. We investigated the evolutionary and developmental origins of rods in two divergent vertebrate retinae. In mice, we discovered genetic and epigenetic vestiges of short wavelength cones in developing rods and cell lineage tracing validated the genesis of rods from S-cones. Curiously, rods did not derive from S-cones in zebrafish. Our study illuminates several questions regarding the evolution of duplex retina and supports the hypothesis that, in mammals, the S-cone lineage was recruited via the Maf-family transcription factor NRL to augment rod photoreceptors. We propose that this developmental mechanism allowed the adaptive exploitation of scotopic niches during the nocturnal bottleneck early in mammalian evolution. Overall design: GFP positive cells from Nrlp-GFP or Nrlp-GFP;Nrl-KO mouse retinas at post-natal ages P2, P4, P6, P10, P14, and P28 were isolated by flow sorting by FACSAria II (Becton Dickinson). Total RNA was extracted by Trizol LS (Life Technologies) and analyzed by 2100 Bioanalyzer (Agilent Technologies Genomics). High quality of total RNA (RIN: >7.0) was subjected to sequencing library construction using 20 ng of total RNA as input. Libraries were constructed using a stranded modification of the Illumina TruSeq mRNA (Brooks, et al. Meth Mol Biol 2012). Each library was single-end sequenced in an independent lane of a GAIIx at a length of 76 bases. Fastq files were generated from reads passing chastity filter.

Publication Title

Recruitment of Rod Photoreceptors from Short-Wavelength-Sensitive Cones during the Evolution of Nocturnal Vision in Mammals.

Sample Metadata Fields

Specimen part, Cell line, Subject

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accession-icon SRP014008
RNA expression in Drosophila melanogaster mutants lacking HP1a
  • organism-icon Drosophila melanogaster
  • sample-icon 4 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2000

Description

mRNA expression levels were determined by NGS for wildtype larvae as well as for larvae lacking HP1a [Su(var)205^04/Su(var)205^05 transheterozygotes]. Overall design: RNA samples from wildtype (OR) and HP1a mutant third instar larvae were examined, using duplicate biological samples and Illumina NGS.

Publication Title

Enrichment of HP1a on Drosophila chromosome 4 genes creates an alternate chromatin structure critical for regulation in this heterochromatic domain.

Sample Metadata Fields

Subject

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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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