Filters
Technology
Platform
SRP032928
Homo sapiens
7 Downloadable Samples
IlluminaHiSeq2000
Description
Down syndrome (trisomy 21) is the most common viable chromosomal disorder with intellectual impairment and several other developmental abnormalities. Here, we report the generation and characterization of induced pluripotent stem cells (iPSCs) derived from monozygotic twins discordant for trisomy 21 in order to eliminate the effects of the variability of genomic background. The alterations observed by genetic analysis at the iPSC level and at first approximation in early development illustrate the developmental disease transcriptional signature of Down syndrome. Moreover, we observed an abnormal neural differentiation of Down syndrome iPSCs in vivo when formed teratoma in NOD-SCID mice, and in vitro when differentiated into neuroprogenitors and neurons. These defects were associated with changes in the architecture and density of neurons, astroglial and oligodendroglial cells together with misexpression of genes involved in neurogenesis, lineage specification and differentiation. Furthermore, we provide novel evidence that dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A) on chromosome 21 likely contribute to these defects. Importantly, we found that targeting DYRK1A pharmacologically or by shRNA results in a considerable correction of these defects. Overall design: mRNA-seq profiling of iPS cells (4 euploid and 3 trisomy 21) derived from fibroblasts of monozygotic twins discordant for trisomy 21
Publication Title
Modelling and rescuing neurodevelopmental defect of Down syndrome using induced pluripotent stem cells from monozygotic twins discordant for trisomy 21.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
In order to identify novel genes regulated by p53, stable line containing tet-on inducible p53 construct was generated and used for gene expression analysis.
Publication Title
Ferroptosis as a p53-mediated activity during tumour suppression.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
Analysis of transcriptome from AR-deleted CARN-derived lines (ADCA) and controls, AR-positive CARN-derived lines (APCA) ADCA and APCA lines at passage 5 or 6 were grown to approximately 70-80% confluency in the presence of DHT, lysed in Trizol and frozen for subsequent molecular analysis Overall design: Total RNA obtained from ADCA and APCA cell lines. Frozen cells in Trizol were processed for RNA isolation and transcriptome analysis using the MagMAX-96 for Microarray kit (Ambion).
Publication Title
Differential requirements of androgen receptor in luminal progenitors during prostate regeneration and tumor initiation.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 32 Downloadable Samples
- Illumina HiSeq 2500, Illumina HiSeq 2000
Description
The juvenile onset of spermatogenesis in mice is analyzed by combining cytological and transcriptomic data in a novel computational analysis, resulting in meiotic substage-specific transcriptomes and the discovery of a transcription factor network that regulates the substages of meiosis. Overall design: Germ cells from testes of individual mice were obtained at two-day intervals from 8 to 18 days post-partum (dpp), with five biological replicates at each age (samples 8_1 through 18_5). Eight stages were discriminated cytologically by combinatorial antibody labeling, and RNA-seq was performed on the same samples. A novel permutation-based maximum covariance analysis (PMCA) method was developed to deconvolve genes into meiotic substages. To verify PMCA derived pachytene/diplotene substage-specific genes, we isolated enriched populations of adult pachytene germ cells (samples rep1 through rep4), followed the same RNA-seq protocol, and compared the PMCA derived substage-specific gene lists to the genes expressed in the pachytene/diplotene enriched germ cells.
Publication Title
Regulatory complexity revealed by integrated cytological and RNA-seq analyses of meiotic substages in mouse spermatocytes.
Sample Metadata Fields
Sex, Age, Cell line, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We hypothesize that cellular mRNAs are incorporated nonselectively into retrovirus particles
Publication Title
Selective and nonselective packaging of cellular RNAs in retrovirus particles.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Zinc-finger genes Fezf1 and Fezf2 encode transcriptional repressors. Fezf1 and Fezf2 are expressed in the early neural stem/progenitor cells and control neuronal differentiation in mouse dorsal telencephalon.
Publication Title
Zinc finger genes Fezf1 and Fezf2 control neuronal differentiation by repressing Hes5 expression in the forebrain.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
Description
We report a novel technique, Affinity-seq, that for the first time identifies both the genome-wide binding sites of DNA-binding proteins and quantitates their relative affinities. We have applied this in vitro technique to PRDM9, the zinc-finger protein that activates genetic recombination, obtaining new information on the regulation of hotspots, whose locations and activities determine the recombination landscape. We identified 31,770 binding sites in the mouse genome for the PRDM9Dom2 variant. Comparing these results with hotspot usage in vivo, we find that less than half of potential PRDM9 binding sites are utilized in vivo. We show that hotspot usage is increased in actively transcribed genes and decreased in genomic regions containing H3K9me2/3 histone marks or bound to the nuclear lamina. These results show that a major factor determining whether a binding site will become an active hotspot and what its activity will be are constraints imposed by prior chromatin modifications on the ability of PRDM9 to bind to DNA in vivo. These constraints lead to the presence of long genomic regions depleted of recombination. Overall design: The terminal zinc finger domain of PRDM9Dom2 (PRDM9?ZnF1Dom2, 412–847 aa), the allele present in C57BL/6J (B6) mice was cloned and tagged with 6His-HALO and then expressed in E. coli. DNA sheared to 180–200 bp is provided in considerable excess to provide competition between DNA binding sites. Following binding, DNA–protein complexes are then isolated on streptavidin beads and the DNA extracted for deep sequencing. Two replicate Affinity-seq samples were sequenced at 100-bp reads using the Illumina HiSeq 2500. Alignments to the mm9 mouse genome were obtained utilizing BWA v1.2.3 with default parameters and reads which failed to align to unique positions in the genome were discarded. Peaks were called individually for the two replicates with MACS2 at a p value threshold of 0.01 utilizing a control dataset obtained by sequencing the input DNA and subsequently compared, leading ultimately to combining the two replicates for definitive analysis.
Publication Title
Affinity-seq detects genome-wide PRDM9 binding sites and reveals the impact of prior chromatin modifications on mammalian recombination hotspot usage.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 108 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
In this study that was specifically designed to identify early stages of glaucoma in DBA/2J mice, we used genome-wide expression profiling and a series of computational methods. Our methods successfully subdivided eyes with no detectable glaucoma by conventional assays into molecularly defined stages of disease. These stages represent a temporally ordered sequence of glaucoma states. Using an array of tools, we then determined networks and biological processes that are altered at these early stages. Our strategy proved very sensitive, suggesting that similar approaches will be valuable for uncovering early processes in other complex, later-onset diseases. Early changes included upregulation of both the complement cascade and endothelin system, and so we tested the therapeutic value of separately inhibiting them. Mice with a mutation in the complement component 1a gene (C1qa) were robustly protected from glaucoma with the protection being among the greatest reported. Similarly, inhibition of the endothelin system was strongly protective. Since EDN2 is potently vasoconstrictive and was produced by microglial/macrophages, our data provide a novel link between these cell types and vascular dysfunction in glaucoma. Targeting early events such as the upregulation of the complement and endothelin pathways may provide effective new treatments for human glaucoma.
Publication Title
Molecular clustering identifies complement and endothelin induction as early events in a mouse model of glaucoma.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Although host genetics influences susceptibility to tuberculosis, few genes determining disease outcome have been identified. We hypothesized that macrophages from individuals with different clinical manifestations of tuberculosis infection would have distinct gene expression profiles, and that polymorphisms in these genes may also be associated with susceptibility to TB.
Publication Title
Identification of tuberculosis susceptibility genes with human macrophage gene expression profiles.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The entire small intestine was obseved by balloon endoscopy. Biopsy specimens were taken from jejunum, ileum and colon, respectively.
Publication Title
Reduced Human α-defensin 6 in Noninflamed Jejunal Tissue of Patients with Crohn's Disease.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples