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SRP081553
Danio rerio
16 Downloadable Samples
IlluminaHiSeq2500
Description
The RNA-binding protein FUS is implicated in transcription, alternative splicing of neuronal genes and DNA repair. Mutations in FUS have been linked to human neurodegenerative diseases such as ALS (amyotrophic lateral sclerosis). We genetically disrupted fus in zebrafish (Danio rerio) using the CRISPR-Cas9 system. The fus knockout animals are fertile and did not show any distinctive phenotype. Mutation of fus induces mild changes in gene expression on the transcriptome and proteome level in the adult brain. We observed a significant influence of genetic background on gene expression and 3’UTR usage, which could mask the effects of loss of Fus. Unlike published fus morphants, maternal zygotic fus mutants do not show motoneuronal degeneration and exhibit normal locomotor activity. Overall design: We performed paired-end sequencing (100bp reads) of the polyA+ transcriptome from brains of five individuals with Fus-/- genotype and four with Fus wild type genotype. Note on RNA-Seq replicates: after performing first RNA sequencing on four replicates of Fus-/- and WT (labeled with the prefix "Sample_imb_ketting_2014_13_") we received a notice from Illumina stating a problem with the library preparation kit lot that was used to prepare the libraries. Due to that, we performed RNA sequencing a second time, using the same input RNA, except for the Fus knockout replicate #3, because there was not enough input RNA left. Instead, a different Fus knockout replicate (#1) was sequenced. However, we compared the mapped reads from sequencing run 1 and sequencing run 2 using plotCorrelaction from DeepTools, and the samples are highly correlated (at least 0.97 and 0.95, Spearman and Pearson correlation respectively). Therefore, we considered first ("Sample_imb_ketting_2014_13_") and second sequencing runs as technical replicates.
Publication Title
Characterization of genetic loss-of-function of Fus in zebrafish.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 28 Downloadable Samples
Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
This study was designed to investigate gene expression in kidneys of adult female Sabra rats (SBH/y and SBN/y rat strains) with two indwelling kidneys or after uni-ninephrectomy, seeking those genes that are differentially expressed between the two strains, and between animals with one or two kidneys. SBH/y after uninephrectomy develop proteinuria to a much greater extent than SBN/y. The study was performed as part of an overall effort to detect the genes that are associated with the pathophysiology of proteinuria.
Publication Title
Geno-transcriptomic dissection of proteinuria in the uninephrectomized rat uncovers a molecular complexity with sexual dimorphism.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 55 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
MiRNAs are essential mediators of many biological processes. The aim of this study was to investigate the dynamics of miRNA-mRNA regulatory networks during exercise and subsequent recovery period.
Publication Title
Dynamically regulated miRNA-mRNA networks revealed by exercise.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Transcriptional profiling of histone methyltransferase SUV39H1-selective small molecule inhibitor F5446-induced genes in human colon carcinoma cells. Tumor cells were treated with F5446 for 48h and used for RNA isolation. The treated cells were compared to untreated control cells. The objective is to identify genes that are regulated by H3K9me3 in the metastatic human colon carcinoma cells.
Publication Title
SUV39H1 regulates human colon carcinoma apoptosis and cell cycle to promote tumor growth.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Huntingtons disease (HD) is an incurable hereditary neurodegenerative disorder, which manifests itself as a loss of GABAergic medium spiny (GABA MS) neurons in the striatum and caused by an expansion of the CAG repeat in exon 1 of the huntingtin gene. There is no cure for HD, existing pharmaceutical can only relieve its symptoms. Here, induced pluripotent stem cells were established from patients with low CAG repeat expansion in the huntingtin gene, and were then efficiently differentiated into GABA MS-like neurons under defined culture conditions. Analysis of differentially expressed genes between Huntingtons disease and wild type iPSCs derived GABA MS-like neurons has been performed.
Publication Title
Manifestation of Huntington's disease pathology in human induced pluripotent stem cell-derived neurons.
Sample Metadata Fields
Age, Specimen part
View Samples- Caenorhabditis elegans
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
In this study, we analyzed the impact of a mutation in the wrn-1 gene compared to wild type worms and the dietary supplementation of vitamin C on the global mRNA expression of the whole C. elegans by the RNA-seq technology. Overall design: Whole C. elegans mRNA profiles at the L4 stage of wild type and wrn-1(gk99) mutant animals treated with or without 10 mM ascorbate were generated by deep sequencing, in triplicate, using the HiSeq 2000 machine form Illumina. Detailed statistics on the quality of the reads were calculated with FastQC (http://www.bioinformatics.babraham.ac.uk/projects/fastqc/). The 50 base pairs raw sequences were aligned on the C. elegans ce10/W220 genome with TopHat using the Ensembl annotations provided with the Illumina iGenomes. The htseq-count software (http://www-huber.embl.de/users/anders/HTSeq) was used to count the number of reads aligned to each gene. These counts were then normalized relative to the sequencing depth with DESeq.
Publication Title
Expression profile of Caenorhabditis elegans mutant for the Werner syndrome gene ortholog reveals the impact of vitamin C on development to increase life span.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 334 Downloadable Samples
- IlluminaGenomeAnalyzerII
Description
Based on preliminary data demonstrating that macrophages are critical regulators of Helicobacter pylori colonization and gastric pathology in mice, we sought to investigate how macrophages may serve as bacterial reservoirs of intracellular H. pylori. Overall design: BMDM were isolated from WT and PPARg-/- mice and cultured with M-CSF for 7 days to promote macrophage differentiation. Fully differentiation macrophages were challenged with H. pylori strains SS1 at an MOI of 10 for 15 minutes. Extracellular bacteria was then eliminated by gentamycin treatment. Cells were collected at 0, 60, 120, 240, 360 and 720 minutes post gentamycin treatment to ascertain whole transcriptome differential gene expression during infection.
Publication Title
Identification of new regulatory genes through expression pattern analysis of a global RNA-seq dataset from a Helicobacter pylori co-culture system.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
While disease recurrence remains the outstanding clinical challenge in acute myeloid leukemia (AML), the basis of relapse remains poorly characterized and thereby preventing effective therapeutic targeting. We performed gene expression analysis of human AML patient samples in addition to in vitro and in vivo assays of leukemic cell survival and self-renewal using xenograft modeling. These molecular and functional analyses afforded the identification of unique target genes that support recurrence. Preclinical modeling using these novel targets provided proof-of-principle for combination therapies towards more effective and durable suppression of AML regrowth.
Publication Title
Identification of Chemotherapy-Induced Leukemic-Regenerating Cells Reveals a Transient Vulnerability of Human AML Recurrence.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Increasing evidence suggests that cancer arises from cells that are capable of initiating and sustaining neoplastic tissue growth, termed cancer stem cells (CSCs). Of central scientific and clinical relevance, cells with CSC properties are enriched for chemo- and radiation resistance and therefore may represent a population of cells that must be therapeutically targeted to prevent cancer recurrence/relapse 1. Human CSCs were first isolated in neoplastic hematopoietic tissue that manifests leukemias such as adult acute myeloid leukemia (AML) 2. AML stem cells represent a benchmark model of human CSC biology, ultimately motivating foundational studies leading to the identification of CSCs from solid tumours such as breast and colon 3. Independent of tissue type, a consistent feature of CSCs is their uncontrolled self-renewal capacity and differentiation blockade that have been commonly related to aberrant activation of pro-oncogenic events such as dysregulation of CBP/p300 transcriptional regulation involving -catenin 4. However, the transcriptional networks involving CBP/p300/-catenin complex have been shown to be equally critical to maintain normal stem cell (SCs) self-renewal for tissue homeostasis and regeneration 5. Here, we identify Sam68 as a distinct target that affords the ability to uniquely regulate CBP mediated transcription in human CSCs. Using a small molecule that targets Sam68, we reveal that shifting its affinity for CBP disrupts CBP/-catenin complexes, leading to immediate changes in histone H3 (K14 and K18) acetylation. Chemical targeting of Sam68 induced global changes in transcriptional programs of patient AML cells involving apoptosis and differentiation and was able to uniquely reduce neoplastic self-renewal of human CSCs in an in vivo model of patient specific acute myeloid leukemia (AML). Our study establishes an approach whereby the CBP/-catenin transcriptome can be uniquely targeted via Sam68 based vulnerability of CSCs that impacts neoplastic differentiation and self-renewal.
Publication Title
Sam68 Allows Selective Targeting of Human Cancer Stem Cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Global gene expression comparison between mesenchymal stem cells (MSCs) purified from the BM of AML patients versus healthy donors.
Publication Title
Acute myeloid leukaemia disrupts endogenous myelo-erythropoiesis by compromising the adipocyte bone marrow niche.
Sample Metadata Fields
Specimen part, Disease stage
View Samples