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Homo sapiens
78 Downloadable Samples
Illumina HiSeq 2500, Illumina HiSeq 3000, NextSeq 500
Description
Interrogation and control of cellular fate and function using optogenetics is providing revolutionary insights into biology. Optogenetic control of cells is achieved by coupling genetically encoded photoreceptors to cellular effectors and enables unprecedented spatiotemporal control of signaling processes. Here, a fast and reversibly switchable photoreceptor is used to tune the mechanical properties of polymer materials in a fully reversible, wavelength-specific, and dose- and space-controlled manner. By integrating engineered cyanobacterial phytochrome 1 into a polyethylene glycol matrix, hydrogel materials responsive to light in the cell-compatible red/far-red spectrum are synthesized. These materials are applied to study in human mesenchymal stem cells how different mechano-signaling pathways respond to changing mechanical environments, and to control the migration of primary immune cells in 3D. This optogenetics-inspired matrix allows addressing fundamental questions of how cells react to dynamic mechanical environments. Further, remote control of such matrices could create new opportunities for tissue engineering or provide a basis for optically stimulated drug depots. Overall design: Analysis of global gene expression changes due to differences in the mechanical properties of the phytochrome-based hydrogels
Publication Title
Phytochrome-Based Extracellular Matrix with Reversibly Tunable Mechanical Properties.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 20 Downloadable Samples
- Illumina HiSeq 2000
Description
Purpose: The outer blood-retina barrier is established through the coordinated terminal maturation of the retinal pigment epithelium (RPE), fenestrated choroid endothelial cells (ECs) and Bruch’s membrane, a highly organized basement membrane that lies between both cell types. Here we study the contribution of choroid ECs to this process by comparing their gene expression profile before (P5) and after (P30) the critical postnatal period when mice acquire mature visual function. Methods: ECs from P5 and P30 mice were labeled in vivo by retro-orbital injection of fluorescently-labeled anti-VE-Cadherin. After 10 minutes, mice were euthanized, eyeballs were enucleated and the anterior segment was discarded. After removal of the neural retina, RPE/choroid was mechanically dissected from the sclera and digested. ECs were isolated by flow cytometry and processed immediately for RNA extraction. Results: Transcriptome analyses show that whereas P5 choroid EC transcriptome is preferentially enriched in cell cycle- and chromosome-related transcripts, reflecting an immature phenotype, the transcriptome of adult (P30) choroid ECs is enriched in genes encoding proteins involved in ‘biological adhesion’, including a variety of extracellular matrix (ECM)-related genes. Conclusion: these results strongly suggest that mature choroid ECs actively participate in extracellular matrix assembly and regulation. Overall design: Transcriptome of choroid ECs isolated from P5 and P30 mice (3 independent isolations, 7 animals per isolation) was determined using the Illumina HiSeq2000 platform. Upon quality control using FastQC, raw reads were aligned to the mouse genome (mm9) using TopHat with default parameters. CuffLinks with GC and upper quartile normalization was then used to calculate normalized expression levels.
Publication Title
Concerted regulation of retinal pigment epithelium basement membrane and barrier function by angiocrine factors.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 18 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Medulloblastoma (MB) is the most common malignant brain tumor in children, among whom overexpression or amplification of MYC oncogenes has been associated with poor clinical outcome. Although the MYC functions during normal development and oncogenesis in various systems have been extensively investigated, the transcriptional targets mediating MYC effects in MB are still elusive. Their identification and roles during MB onset and progression are important and will ultimately suggest novel potential therapeutic targets. cDNA microarray analysis was used to compare the effects of overexpressing and silencing MYC on the transcriptome of a MB-derived cell line. We identified 209 genes with potential relevance to MYC-dependent cellular responses in MB. Among the MYC-responsive genes, we found members of the bone morphogenetic protein (BMP) signaling pathway, which plays a crucial role during the development of the cerebellum. In particular, the cytokine gene BMP7 was identified as a direct target of MYC in MB cells. Similar to the effect induced by BMP7 silencing by siRNA, the use of a small-molecule inhibitor of the BMP/SMAD signaling pathway reduced cell viability in a panel of MB cells. Altogether, our findings indicate that high MYC levels drive BMP7 expression in MB to induce pro-survival and pro-proliferative cellular pathways. This observation suggests that targeting the BMP/SMAD pathway may be a new therapeutic concept for the treatment of childhood MB.
Publication Title
Bone morphogenetic protein-7 is a MYC target with prosurvival functions in childhood medulloblastoma.
Sample Metadata Fields
Specimen part, Cell line
View Samples
GSE1919- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U95A Array (hgu95a)
Description
Rheumatoid arthritis (RA) is a chronic, inflammatory joint disease of unknown etiology and pronounced inter-patient heterogeneity. To characterize RA at the molecular level and to uncover key pathomechanisms, we performed whole-genome gene expression analyses. Synovial tissues from rheumatoid arthritis patients were compared to those from osteoarthritis patients and to normal donors.
Publication Title
Molecular signatures and new candidates to target the pathogenesis of rheumatoid arthritis.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 24 Downloadable Samples
- NextSeq 500, Illumina HiSeq 2000
Description
We studied the synaptic activity-regulated gene expression response in the human genetic background using cultured human iPSC-derived (hiPSCd) neuronal networks and networks of hiPSCd neurons mixed with mouse primary neurons. Our results confirm that genetic changes affect the synaptic activity-regulated gene program, proposing a functional mechanism how they have driven evolution of human cognitive abilities. Overall design: We compared RNA profiles of untreated hiPSCd neurons and hiPSCd neurons treated with bicuculline and 4-aminopyridine for 1 or 4 hours. Samples were collected from hiPSCd neuron-only cultures and from co-cultures of hiPSCd neurons and mouse primary hippocampal neurons.
Publication Title
Networks of Cultured iPSC-Derived Neurons Reveal the Human Synaptic Activity-Regulated Adaptive Gene Program.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Analysis of early and late changes in the mouse peritoneal cells in response to E. coli induced sepis. Result provide an insight into the molecular function and pathways expressed at these different time points.
Publication Title
Transcriptomic analysis of peritoneal cells in a mouse model of sepsis: confirmatory and novel results in early and late sepsis.
Sample Metadata Fields
Sex, Treatment
View Samples- Arabidopsis thaliana
- 24 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
The first described feedback loop of the Arabidopsis circadian clock is based on reciprocal regulation between TOC1 and CCA1/LHY. CCA1 and LHY are MYB transcription factors that bind directly to the TOC1 promoter to negatively regulate its expression. Conversely, the activity of TOC1 has remained less well characterized. Genetic data supports that TOC1 is necessary for the reactivation of CCA1/LHY, but there is little description of its biochemical function. Here we show that TOC1 occupies specific genomic regions in the CCA1 and LHY promoters. Purified TOC1 binds directly to DNA through its CCT domain, which is similar to known DNA binding domains. Chemical induction and transient overexpression of TOC1 in Arabidopsis seedlings cause repression of CCA1/LHY expression demonstrating that TOC1 can repress direct targets, and mutation or deletion of the CCT domain prevents this repression showing that DNA binding is necessary for TOC1 action. Furthermore, we use the Gal4/UAS system in Arabidopsis to show that TOC1 acts as a general transcriptional repressor, and that repression activity is in the Pseudoreceiver (PR) domain of the protein. To identify the genes regulated by TOC1 on a genomic scale, we couple TOC1 chemical induction with microarray analysis and identify new potential TOC1 targets and output pathways. Together these results define the biochemical action of the core clock protein TOC1 and refine our perspective on how plant clocks function.
Publication Title
Arabidopsis circadian clock protein, TOC1, is a DNA-binding transcription factor.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 4 Downloadable Samples
- Drosophila Gene 1.1 ST Array (drogene11st)
Description
Analysis of Drosophila melanogaster early embryos (pre-zygotic genome activation) following the germ line-specific depletion of the dMLL3/4 histone methyltransferase (also known as Trr). These results provide insight into the molecular mechanisms responsible for the assembly of the zygotic genome at fertilization.
Publication Title
The Trithorax group protein dMLL3/4 instructs the assembly of the zygotic genome at fertilization.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 3 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
The goal of this gene expression profiling experiment was to identify the entire set of transcription factors expressed during late pupal wing development (~80h APF) when pigmentation genes are expressed
Publication Title
Emergence and diversification of fly pigmentation through evolution of a gene regulatory module.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 147 Downloadable Samples
- Illumina HiSeq 2000
Description
The transcriptional response to many widely used drugs and its modulation by genetic variability is poorly understood. Here we present an analysis of RNAseq profiles from heart tissue of 18 inbred mouse strains treated with the ß-blocker atenolol (ATE) and the ß-agonist isoproterenol (ISO). Differential expression analyses revealed a large set of genes responding to ISO (n=1770 at FDR=0.0001) and a comparatively small one responding to ATE (n=23 at FDR=0.0001). At a less stringent definition of differential expression, the transcriptional responses to these two antagonistic drugs are reciprocal for many genes, with an overall anti-correlation of r= -0.3. This trend is also observed at the level of most individual strains even though the power to detect differential expression is significantly reduced. The inversely expressed gene sets are enriched with genes annotated for heart-related functions. Modular analysis revealed gene sets that exhibited coherent transcription profiles across some strains and/or treatments. Correlations between such modules and a broad spectrum of cardiovascular traits are stronger than expected by chance. This provides evidence for the overall importance of transcriptional regulation for these organismal responses and explicits links between co-expressed genes and the traits they are associated with. Gene set enrichment analysis of differentially expressed groups of genes pointed to pathways related to heart development and functionality. Our study provides new insights into the transcriptional response of the heart to perturbations of the ß-adrenergic system, implicating several new genes that had not been associated to this system previously. Overall design: Cardiac mRNA expression profiles of the various inbred mouse strains were examined either under baseline condition (control) or in response to chronic administration of isoproterenol or atenolol at 10 mg/kg per day for 2 weeks. Expression data were produced by RNA-sequencing, in triplicates, using the HiSeq 2000 Illumina platform. Only males, aged ten to twelve weeks on average, were included in the experimental protocol. Mouse ID numbers refer to those described in Berthonneche C. et al. PLoS One. 2009 Aug 12;4(8):e6610 (doi: 10.1371/journal.pone.0006610. PMID: 19672458). Corresponding individual phenotypic values, in particular heart rate, systolic blood pressure, electrocardiogaphic measurements and heart weight are available in dataset "maurer1" of the Mouse Phenome Database (http://phenome.jax.org/). Preparation of the sequencing libraries, RNA-sequencing and RNA expression quantitations were performed by the BGI.
Publication Title
RNAseq analysis of heart tissue from mice treated with atenolol and isoproterenol reveals a reciprocal transcriptional response.
Sample Metadata Fields
Sex, Specimen part, Treatment, Subject
View Samples