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Mus musculus
9 Downloadable Samples
Illumina HiSeq 2000
Description
Purpose: Guided by an in silico combination of microRNA (miRNA) target prediction, analysis of transcriptomic changes in 137 human diseases, and advanced gene network modeling, we predicted the miR-130/301 family of miRNAs as a shared regulator of a fibrotic gene network across human diseases, thus orchestrating broad control over disease manifestation. The goals of this study are to compare the lung mRNA profile of mouse model of Pulmonary hypertension, one of the most fibrotic pathology uncovered by our in silico prediction, treated with an inhibitor of miR-130/301 (Short-130) to mice treated with a control inhibitor (Short-NC). Methods: Eight-week-old mice (C57BL/6) were injected with SU5416 (20 mg/kg/dose; Sigma-Aldrich), followed by exposure to normobaric hypoxia (10% O2; OxyCycler chamber, Biospherix Ltd.) for 2 weeks. After 2 weeks and confirmation of PH development in 5 mice (right heart catheterization), mice were further treated with 3 intrapharyngeal injections (every 4 days) of control or miR-130/301 shortmer oligonucleotides, designed as fully modified antisense oligonucleotides complementary to the seed sequence of the miR-130/301 miRNA family (10 mg/kg/dose; Regulus). Specifically, the control and miR-130/301 shortmer oligonucleotides were nontoxic, lipid-permeable, high-affinity oligonucleotides. The miR-130/301 shortmer carried a sequence complementary to the active site of the miR-130/301 miRNA family, containing a phosphorothioate backbone and modifications (fluoro-, methoxyethyl, and bicyclic sugar) at the sugar 2' position. Three days after the last injection, right heart catheterization was performed followed by harvesting of lung tissue for RNA extraction. Lung mRNA profiles of those mice or control mice (Normoxia+SU5416) were generated by deep sequencing, in triplicate, using Illumina HiSeq 2000. The sequence reads that passed quality filters were analyzed at the gene-level count. The gene level counts were then normalized with the R/Bioconductor package limma using the voom /variance stabilization method. The data were quality controlled for outliers using principal component analysis (PCA). Differential expression analysis between transcriptome profiles of experimental groups was performed using the R / Bioconductor package limma. Results: Transcriptomic analyses of whole lung from mice with hypoxia+SU5416-induced PH revealed a generalized de-repression of miR-130/301 targets by Short-130 treatment. Importantly, although whole lung transcriptomics likely captured only a subset of the miR-130/301 targets affecting the diseased pulmonary vasculature, pathway enrichment nonetheless revealed pronounced representation of several pathways known to be involved in fibrosis. Thus, the miR-130/301 family indeed induces a programmatic shift at the molecular level toward the fibrotic pathophenotype in vivo Overall design: Whole lung mRNA profiles of Normoxia (Control) and hypoxia+SU5416-induced PH mice treated with Short-NC or Short-130 were generated by deep sequencing, in triplicate, using Illumina HiSeq 2000.
Publication Title
Matrix Remodeling Promotes Pulmonary Hypertension through Feedback Mechanoactivation of the YAP/TAZ-miR-130/301 Circuit.
Sample Metadata Fields
No sample metadata fields
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GSE6460- Homo sapiens
- 7 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The identity of cells that establish the hematopoietic microenvironment (HME) in human bone marrow (BM), and of skeletal ("mesenchymal") stem cells (SSCs) found in BM stroma, have long remained elusive. We show that MCAM/CD146-expressing, subendothelial cells in human BM stroma are both the self-renewing SSCs and the cells that transfer the HME at heterotopic sites upon transplantation.
Publication Title
Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 27 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
With the goal of specifically dissecting the toxicogenomic signatures of the helper-dependent (HD) human (HAd5) and canine (CAV-2) adenovirus, the VSV-G-pseudotyped SIN HIV-1 (LV) and the Adenoviral-associated vector 2/9 for human neurons (AAV2/9), we transduced a bona fide human neuronal system with HD-HAd5, HD-CAV-2, LV and AAV2/9, we analysed the transcriptional response of more than 47,000 transcripts using gene chips.
Publication Title
Differentiated neuroprogenitor cells incubated with human or canine adenovirus, or lentiviral vectors have distinct transcriptome profiles.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Brain gene transfer using viral vectors will likely become a therapeutic option for several disorders. Helper-dependent (HD) canine adenovirus type 2 vectors (CAV-2) are well suited for this goal. Indeed, these vectors are poorly immunogenic, efficiently transduce neurons, are retrogradely transported to afferent structures in the brain, and lead to long-term transgene expression. CAV-2 vectors have been exploited to unravel behavior, cognition, neural networks, axonal transport and therapy for orphan diseases. Here we describe the HD-CAV-2 vector induced transcriptional response of human dopaminergic neurospheres derived from midbrain progenitors. In this 3D model system, brain cell functions and dynamics mimic several aspects the dynamic nature of human brain. With the goal of better understanding and characterizing HD CAV-2 for brain therapy, we analyzed the transcriptomic modulation induced by HD-CAV-2 in this brain model system.
Publication Title
Transcriptional Response of Human Neurospheres to Helper-Dependent CAV-2 Vectors Involves the Modulation of DNA Damage Response, Microtubule and Centromere Gene Groups.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
A widely shared view reads that 'MSCs' are ubiquitous in human connective tissues, can be defined by a common in vitro phenotype, share a skeletogenic potential as assessed by in vitro differentiation assays, and coincide with the ubiquitous 'pericytes.' Using stringent in vivo differentiation assays and transcriptome analysis, we show here that human cell populations from different anatomical sources, which would all be regarded as 'MSCs' based on these criteria and assumptions, actually differ widely in their transcriptomic signature and in vivo differentiation potential. In contrast, they share the capacity to guide the assembly of functional microvessels in vivo, regardless of their anatomical source, or in situ identity as perivascular or circulating cells. This analysis further reveals that muscle 'pericytes,' which are not spontaneously osteo-chondrogenic as previously claimed, may indeed coincide with an ectopic perivascular subset of committed myogenic cells similar to satellite cells. Cord blood-derived stromal cells, on the other hand, display the unique capacity to form cartilage in vivo spontaneously, in addition to an assayable osteogenic capacity. These data suggest the need to revise current misconceptions on the origin and function of so-called 'MSCs,' with important applicative implications. The data also support the view that rather than a uniform class of 'MSCs,' different mesoderm derivatives include distinct classes of tissue-specific committed progenitors, likely of different developmental origin.
Publication Title
No Identical "Mesenchymal Stem Cells" at Different Times and Sites: Human Committed Progenitors of Distinct Origin and Differentiation Potential Are Incorporated as Adventitial Cells in Microvessels.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 63 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
LITAF, a BCL6 target gene, regulates autophagy in mature B-cell lymphomas.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Danio rerio
- 14 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Dynamic nucleosome organization at hox promoters during zebrafish embryogenesis.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Danio rerio
- 14 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
Nucleosome arrangement in promoter regions has been shown to play an important role in gene regulation. Genome wide studies in yeast, flies, worms, mammalian ES and transformed cell lines have found well positioned nucleosomes with an area of nucleosome depletion flanking transcription start sites. This Nucleosome arrangement has been shown to be dependent on sequence (cis-regulatory factors), DNA binding factors (trans-regulatory factors) and ATP-dependant chromatin modifiers. However, little is understood about how the nascent embryonic genome positions nucleosomes during development. This is particularly intriguing since the embryonic genome undergoes a whole scale rechromatinization event upon fusion of sperm and oocyte. Using four stages of early embryonic zebrafish development we map nucleosome positions at the promoter region of 34 zebrafish hox genes. We find that nucleosome arrangement at the hox promoters is a dynamic process which happens over several stages. We also find evidence that trans-regulatory factors play a greater role in nucleosome positioning over cis-regulatory elements. Finally we provide evidence that transcriptional activation is the driving force behind the arrangement of nucleosomes at the promoters of hox gene during early development.
Publication Title
Dynamic nucleosome organization at hox promoters during zebrafish embryogenesis.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Danio rerio
- 6 Downloadable Samples
- IlluminaHiSeq2000
Description
Identification of genes that are differentially-expressed in dusp2um287/um287;dusp6um286/um286 mutant embryos compared to wildtype Overall design: Total RNA was extracted from pools of dechrionated, deyolked wildtype and dusp2um287/um287;dusp6um286/um286 embryos at 18hpf using the RNeasy Mini Kit (Qiagen). Three libraries from wildtype embryos and three libraries from dusp2um287/um287;dusp6um286/um286 embryos were then generated from 3mg RNA using the TruSeq Stranded mRNA Library Prep Kit (Illumina). All libraries were analyzed for quality on a bioanalyzer prior to sequencing (Agilent 2100 BioAnalyzer).
Publication Title
A parental requirement for dual-specificity phosphatase 6 in zebrafish.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 55 Downloadable Samples
- Illumina HiSeq 2500, Illumina HiSeq 3000
Description
Using different surface markers it has been possible to isolate lymphoid lineage-biased progentors and test their potential in vivo and in vitro. Here we apply single cell sequencing of lymphoid progenitors to obtain further insights into differentiation and commitment to the lymphoid lineage. Overall design: Single cells from the bone marrow from various stages during lymphoid differentiation were sorted into 384-well plates based on their surface marker expression of Flt3, Sca-1 and c-Kit and processed using a modified version of the CEL-Seq2 protocol (Hashimshony et al. 2016, Genome Biology, DOI: 10.1186/s13059-016-0938-8). In addition the original version of the CEL-Seq2 protoco and thel modified versions with different volume reductions and were compared using murine embryonic stem cells.
Publication Title
FateID infers cell fate bias in multipotent progenitors from single-cell RNA-seq data.
Sample Metadata Fields
Specimen part, Cell line, Subject
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