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SRP075353
Mus musculus
13 Downloadable Samples
Illumina HiSeq 2000, Illumina HiSeq 2500
Description
Polycomb-mediated gene repression plays an important role in adult stem cell maintenance. We knocked out (using the inducible AhCre-LoxP system) Polycomb genes Eed and Ezh2 in the intestine for 6 weeks, after which crypts - the small intestinal stem cell zone - were harvested and RNA sequenced. We found Wnt, Notch and cell cycle pathways to be affected in Eed knockout (KO) but not Ezh2 KO crypts. Direct targets of Eed were determined by comparing this data with ChIP-sequencing. Overall design: Small intestinal crypt mRNA profiles of 6 weeks-induced 12 weeks old Eed KO, Ezh2 KO and WT mice (all triplicates) as well as 10 days-induced Eed KO and WT organoids (duplicates) were generated by RNA sequencing over two runs and using IlluminaHiseq2000 and Hiseq2500.
Publication Title
Deletion of Polycomb Repressive Complex 2 From Mouse Intestine Causes Loss of Stem Cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Rattus norvegicus
- 9 Downloadable Samples
Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Lung alveolarization is a complex process that involves interactions between several cell types and leads to considerable increase in gas-exchange surface area. The step designated secondary septation includes elastogenesis from interstitial fibroblasts.
Publication Title
Gene expression profiling in lung fibroblasts reveals new players in alveolarization.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
In Rspondin-based 3D cultures, Lgr5 stem cells from multiple organs form ever-expanding epithelial organoids that retain their tissue identity. We report the establishment of tumor organoid cultures from 20 consecutive colorectal (CRC) patients. For most, organoids were also generated from adjacent normal tissue. The organoids closely resemble the original tumor. The spectrum of genetic changes observed within the 'living biobank' agrees well with previous large-scale mutational analyses of CRC. Gene expression analysis indicates that the major CRC molecular subtypes are represented. Tumor organoids are amenable to robotized, high-throughput drug screens allowing detection of gene-drug associations. As an example, a single organoid culture was exquisitely sensitive to Wnt secretion (porcupine) inhibitors and carried a mutation in the negative Wnt feedback regulator RNF43 (rather than in APC). Organoid technology may fill the gap between cancer genetics and patient trials, complement cell line- and xenograft-based drug studies and allow personalized therapy design.
Publication Title
Prospective derivation of a living organoid biobank of colorectal cancer patients.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 21 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Molecular mechanisms that are responsible for the development of human skin epithelial cells are not completely understood so far. As a consequence, the efficiency to establish a pure skin epithelial cell population from human induced pluripotent stem cells (hiPSC) remains poor. Using an approach including RNA interference and high-throughput imaging of early epithelial cells, we could identify candidate kinases which are involved in skin epithelial differentiation. Among them, we found HIPK4 to be an important inhibitor of this process. Indeed, its silencing increased the amount of generated skin epithelial precursors, increased the amount of generated keratinocytes and improved growth and differentiation of organotypic cultures, allowing for the formation of a denser basal layer and stratification with the expression of several keratins. Our data bring substantial input in the regulation of human skin epithelial differentiation and for improving differentiation protocols from pluripotent stem cells.
Publication Title
An RNAi Screen Reveals an Essential Role for HIPK4 in Human Skin Epithelial Differentiation from iPSCs.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 26 Downloadable Samples
- NextSeq 500
Description
Three different progenitor cell subsets in subcutaneous and visceral adipose tissues derived from 5 obese patients were subjected to AmpliSeq transcriptome profiling. Transcriptomic profiles were analyzed to compare progenitor cell subsets and the impact of subcutaneous and visceral adipose tissue location. Overall design: Transcriptomic profiling of 3 different progenitor cell types in subcutaneous and visceral adipose tissues derived from 5 obese patients (3X2X5=30 samples).
Publication Title
Lobular architecture of human adipose tissue defines the niche and fate of progenitor cells.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Bromodomains have emerged as attractive candidates for the development of inhibitors targeting gene transcription. Inhibitors of the bromo-and-extra-terminal (BET) family recently showed promising activity in diverse disease models. However, the pleiotropic nature of BET proteins regulating tissue specific transcription has raised safety concerns and suggested that attempts should be made for domain-specific targeting. Here we report that RVX-208, a compound currently in phase II clinical trials, is a BET bromodomain inhibitor specific for second bromodomains (BD2). Co-crystal structures revealed binding modes of RVX-208 and its synthetic precursor and fluorescent recovery after photobleaching demonstrated that RVX-208 displaces BET proteins from chromatin. However, gene expression data showed that BD2 inhibition only modestly affects BET-dependent gene transcription. Our data demonstrate the feasibility of specific targeting within the BET family resulting in different transcriptional outcomes and highlight the importance of BD1 in transcriptional regulation
Publication Title
RVX-208, an inhibitor of BET transcriptional regulators with selectivity for the second bromodomain.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Chronic mucocutaneous candidiasis and connective tissue disorder in humans with impaired JNK1-dependent responses to IL-17A/F and TGF-β.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment, Time
View Samples- Rattus norvegicus
- 48 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a)
Description
The size and scope of microarray experiments continue to increase. However, datasets generated on different platforms or at different centres contain biases. Improved techniques are needed to remove platform- and batch-specific biases. One experimental control is the replicate hybridization of a subset of samples at each site or on each platform to learn the relationship between the two platforms. To date, no algorithm exists to specifically use this type of control. LTR is a linear-modelling-based algorithm that learns the relationship between different microarray batches from replicate hybridizations. LTR was tested on a new benchmark dataset of 20 samples hybridized to different Affymetrix microarray platforms. Before LTR, the two platforms were significantly different; application of LTR removed this bias. LTR was tested with six separate data pre-processing algorithms, and its effectiveness was independent of the pre-processing algorithm. Sample-size experiments indicate that just three replicate hybridizations can significantly reduce bias. An R library implementing LTR is available.
Publication Title
LTR: Linear Cross-Platform Integration of Microarray Data.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
To identify the CD4+ T cell cytokines responsible for the proliferation of the Lin-IEL lines CD4+ T cell clone L10, which recognises DQ2-glia-1, one of the immunodominant T cell epitopes in celiac disease, was stimulated for 3 hours in IMDM with plate-bound CD3/CD28-specific (2.5 g/ml each) or control antibodies coated onto 6-well non-tissue culture treated plates. Three independent biological replicates were performed, each time including 6 million Ficoll-purified live cells per condition. RNA was purified from these cells using the RNAeasy mini kit (Qiagen, Venlo, the Netherlands). cDNA was amplified using the Applause WT-Amp system (NuGEN technologies, Bemmel, the Netherlands) and biotin-labelled with the Encore Biotin Module (NuGEN). Human Gene 1.0 ST arrays (Affymetrix, High Wycombe, UK) were employed to quantify global gene expression.
Publication Title
CD4 T-cell cytokines synergize to induce proliferation of malignant and nonmalignant innate intraepithelial lymphocytes.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We used microarrays to compared gene expression profilings in various tumors of the kidney.
Publication Title
Balanced Translocations Disrupting SMARCB1 Are Hallmark Recurrent Genetic Alterations in Renal Medullary Carcinomas.
Sample Metadata Fields
Specimen part
View Samples