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SRP146096
Caenorhabditis elegans
29 Downloadable Samples
Illumina HiSeq 1500
Description
An essential step for understanding the transcriptional circuits that control development and physiology is the global identification and characterization of regulatory elements. Here we present the first map of regulatory elements across the development and ageing of an animal, identifying 42,245 elements accessible in at least one C. elegans stage. Based on nuclear transcription profiles, we define 15,918 protein-coding promoters and 17,918 putative enhancers, and find that both types of element can drive orientation-independent transcription. Additionally, hundreds of promoters produce transcripts antisense to protein coding genes, suggesting involvement in a widespread regulatory mechanism. We find that the accessibility of most elements is regulated during development and/or ageing and that patterns of accessibility change are linked to specific developmental or physiological processes. The map and characterization of regulatory elements across C. elegans life provides a platform for understanding how transcription controls development and ageing. Overall design: Capped nuclear RNA-seq of wild-type and glp-1 was performed to monitor transcription elongation across C. elegans development and ageing. Two biological replicates were done for each time point (six developmental stages and five ageing timepoints).
Publication Title
Chromatin accessibility dynamics across <i>C. elegans</i> development and ageing.
Sample Metadata Fields
Cell line, Subject
View Samples- Caenorhabditis elegans
- 20 Downloadable Samples
- Illumina HiSeq 1500
Description
Repetitive sequences derived from transposons make up a large fraction of eukaryotic genomes and must be silenced to protect genome integrity. Repetitive elements are often found in heterochromatin; however, the roles and interactions of heterochromatin proteins in repeat regulation are poorly understood. Here we show that a diverse set of C. elegans heterochromatin proteins act together with the piRNA and nuclear RNAi pathways to silence repetitive elements and prevent genotoxic stress in the germ line. Mutants in genes encoding HPL-2/HP1, LIN-13, LIN-61, LET-418/Mi-2, and H3K9me2 histone methyltransferase MET-2/SETDB1 also show functionally redundant sterility, increased germline apoptosis, DNA repair defects, and interactions with small RNA pathways. Remarkably, fertility of heterochromatin mutants could be partially restored by inhibiting cep-1/p53, endogenous meiotic double strand breaks, or the expression of MIRAGE1 DNA transposons. Functional redundancy among these factors and pathways underlies the importance of safeguarding the genome through multiple means. Overall design: Synchronized, starved L1 stage worms were grown on NGM plates under one of two conditions. Condition 1: growth was at 20°C (hpl-2, let-418, lin-61, met-2 set-25, and wild-type N2) until the L4 stage and then worms were shifted to 25°C for 15-18 hours until they reached young adult stage. Condition 2: growth was at 15°C (lin-13, prg-1, nrde-2, nrde-2; let-418, and wild-type N2) until the L4 stage, and then worms were shifted to 25°C for 15-18 hours until they reached young adult stage. Worms were then washed off plates, flash frozen in liquid nitrogen, and stored at -80°C until use. RNA was extracted from frozen worms using TriPure (Roche). RNA was purified with Zymo Research RNA Clean and Concentrator-5 (Cambridge Bioscience) following DNase I digestion. Ribosomal RNA was depleted using Ribo-Zero rRNA Removal Kit (Human/Mouse/Rat) (Illumina). Libraries were prepared using the NEBNext Ultra Directional RNA Library Prep Kit for Illumina (New England Biolabs). Two biological replicates were prepared for each strain.
Publication Title
A team of heterochromatin factors collaborates with small RNA pathways to combat repetitive elements and germline stress.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 10 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We have identified a CD57+PD1- CD4 T cell phenotype at the time of transplantation that strongly correlates with subsequesnt development of belatacept-resistant rejection. In this study, we used microarray to determine which genes were upregulated in CD57+ compared to CD57- CD4 T cells.
Publication Title
CD57(+) CD4 T Cells Underlie Belatacept-Resistant Allograft Rejection.
Sample Metadata Fields
Specimen part, Subject
View Samples- Drosophila melanogaster
- 5 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Transcription factors drive organogenesis, from the initiation of cell fate decisions to the maintenance and implementation of these decisions. The Drosophila embryonic salivary gland provides an excellent platform for unraveling the underlying transcriptional networks of organ development because Drosophila is relatively unencumbered by significant genetic redundancy. The highly conserved FoxA family transcription factors are essential for various aspects of organogenesis in all animals that have been studied. Here, we explore the role of the single Drosophila FoxA protein Fork head (Fkh) in salivary gland organogenesis using two genome-wide strategies. A large-scale in situ hybridization analysis reveals a major role for Fkh in maintaining the salivary gland fate decision and controlling salivary gland physiological activity, in addition to its previously known roles in morphogenesis and survival. The majority of salivary gland genes (59%) are affected by fkh loss, mainly at later stages of salivary gland development. We show that global expression of Fkh cannot drive ectopic salivary gland formation. Thus, unlike the worm FoxA protein PHA-4, Fkh does not function to specify cell fate. In addition, Fkh only indirectly regulates many salivary gland genes, which is also distinct from the role of PHA-4 in organogenesis. Our microarray analyses reveal unexpected roles for Fkh in blocking terminal differentiation and in endoreduplication in the salivary gland and in other Fkh-expressing embryonic tissues. Overall, this study demonstrates an important role for Fkh in determining how an organ preserves its identity throughout development and provides an alternative paradigm for how FoxA proteins function in organogenesis.
Publication Title
Genome-wide analysis reveals a major role in cell fate maintenance and an unexpected role in endoreduplication for the Drosophila FoxA gene Fork head.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 1000
Description
Minocycline is a potent modulator of retinal microglia Overall design: Global mRNA expression analysis of CD1 mouse retinas in control, light damage and light damage plus minocycline conditions
Publication Title
Minocycline counter-regulates pro-inflammatory microglia responses in the retina and protects from degeneration.
Sample Metadata Fields
No sample metadata fields
View Samples- Macaca mulatta, Homo sapiens
- 105 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20), Affymetrix Rhesus Macaque Genome Array (rhesus)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Transcriptome analysis of GVHD reveals aurora kinase A as a targetable pathway for disease prevention.
Sample Metadata Fields
Specimen part, Subject
View Samples- Macaca mulatta
- 81 Downloadable Samples
Affymetrix Rhesus Macaque Genome Array (rhesus)
Description
Graft versus host disease (GVHD) is the most common complication of hematopoietic stem cell transplant (HCT). However, our understanding of the molecular pathways that cause this disease remains incomplete, leading to inadequate treatment strategies. To address this, we measured the gene expression profile of non-human primate (NHP) T cells during acute GVHD. This transcriptome analysis enables an unsupervised approach to the identification of targets for disease control using a model with an immune system that closely overlaps with the human and has a high degree of cross-reactivity with human antibody-based therapeutics.
Publication Title
Transcriptome analysis of GVHD reveals aurora kinase A as a targetable pathway for disease prevention.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Graft versus host disease (GVHD) is the most common complication of hematopoietic stem cell transplant (HCT). However, our understanding of the molecular pathways that cause this disease remains incomplete, leading to inadequate treatment strategies. To address this, we measured the gene expression profile of non-human primate (NHP) T cells during acute GVHD (GSE73723). Within these profiles we discovered potentially druggable targets not previously implicated in GVHD, prominently including aurora kinase A (AURKA). In this study, we performed a planned comparison of AURKA gene expression in HCT-recipients with clinical GVHD and compared it to expression in HCT-recipients without clinical GVHD.
Publication Title
Transcriptome analysis of GVHD reveals aurora kinase A as a targetable pathway for disease prevention.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 271 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Pouchitis is a common complication for ulcerative colitis (UC) patients with ileal pouch-anal anastomosis (IPAA) surgery. Similarly to IBD, both innate host factors such as genetics, and environmental stimuli including the tissue-associated microbiome have been implicated in the pathogenesis. In this study, we make use of the IPAA model of inflammatory bowel disease (IBD) to carry out a study associating mucosal host gene expression with the microbiome and corresponding clinical outcomes.
Publication Title
Associations between host gene expression, the mucosal microbiome, and clinical outcome in the pelvic pouch of patients with inflammatory bowel disease.
Sample Metadata Fields
Sex, Disease, Subject
View Samples- Rattus norvegicus
- 27 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Microarrays were used to analyse gene expression underlying early tumourigenesis in Eker rats. Distinct classes of up- and downregulated genes were identified in different preneoplasic lesion vs. microdissected normal (healthy) renal tubules.
Publication Title
Molecular characterization of preneoplastic lesions provides insight on the development of renal tumors.
Sample Metadata Fields
Sex, Specimen part
View Samples