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SRP050116
Caenorhabditis elegans
43 Downloadable Samples
Illumina HiSeq 2000
Description
Longevity mechanisms increase lifespan by counteracting the effects of aging. However, whether longevity mechanisms counteract the effects of aging continually throughout life, or whether they act during specific periods of life, preventing changes that precede mortality is unclear. Here, we uncover transcriptional drift, a phenomenon that describes how aging causes genes within functional groups to change expression in opposing directions. These changes cause a transcriptome-wide loss in mRNA stoichiometry and loss of co-expression patterns in aging animals, as compared to young adults. Using Caenorhabditis elegans as a model, we show that extending lifespan by inhibiting serotonergic signals by the antidepressant mianserin attenuates transcriptional drift, allowing the preservation of a younger transcriptome into an older age. Our data are consistent with a model in which inhibition of serotonergic signals slows age-dependent physiological decline and the associated rise in mortality levels exclusively in young adults, thereby postponing the onset of major mortality. Overall design: In this study set out to measure aging in the transcriptome by determining drift-variance changes with age in C.elegans. We set up three different cohorts of water or mianserin treated animals. The title of each cohort indicates the treatment (e.g. h2o or mia), the concentration (mia2, mia10, mia50), the day when the treatment was started (e.g. d1= day 1 of adulthood) and the day when the sample was collected (e.g. d10= day 10 of adulthood). cohort #1: Celegans was treated with water or mianserin (50uM) on day 1 and RNA was harvested on day1 (water only), d3, d5 and day 10 (file titles: h2o d1/d1, h2o d1/d3, h2o d1/d5, h2o d1/d10, mia50 d1/d3, mia50 d1/d5, mia50 d1/d10) cohort #2: Celegans was treated with mianserin (50uM) starting on day 3, and day 5, RNA was harvested on day 5 or 10 (file titles: mia50 d3/d10, mia50 d5/d10, mia50 d3/d5) cohort #3: Celegans was treated with mianserin 2 uM and 10 uM Mianserin on day 1 and Rna harvested on day 5 (file titles: mia2 d1/d5, mia10 d1/d5)
Publication Title
Suppression of transcriptional drift extends C. elegans lifespan by postponing the onset of mortality.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 3 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Technologies allowing for specific regulation of endogenous genes are valuable for the study of gene functions and have great potential in therapeutics. We created the CRISPR-on system, a two-component transcriptional activator consisting of a nuclease-dead Cas9 (dCas9) protein fused with a transcriptional activation domain and single guide RNAs (sgRNAs) with complementary sequence to gene promoters. We demonstrate that CRISPR-on can efficiently activate exogenous reporter genes in both human and mouse cells in a tunable manner. In addition, we show that robust reporter gene activation in vivo can be achieved by injecting the system components into mouse zygotes. Furthermore we show that CRISPR-on can activate the endogenous IL1RN, SOX2, and OCT4 genes. The most efficient gene activation was achieved by clusters of 3 to 4 sgRNAs binding to the proximal promoters suggesting their synergistic action in gene induction. Significantly, when sgRNAs targeting multiple genes were simultaneously introduced into cells, robust multiplexed endogenous gene activation was achieved. Genome-wide expression profiling demonstrated high specificity of the system.
Publication Title
Multiplexed activation of endogenous genes by CRISPR-on, an RNA-guided transcriptional activator system.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Global mRNA expression was compared between stable and progressive IPF using bronchoalveolar lavage derived mesenchymal stromal cells
Publication Title
Developmental Reprogramming in Mesenchymal Stromal Cells of Human Subjects with Idiopathic Pulmonary Fibrosis.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Original patient tumor is directly implanted in mice xenografts. Tumor is propagated to multiple mice for conduct of 6 arm treatment trials and control. Therapies are selected based on T0 and F0 genomic profiles.
Publication Title
Using a rhabdomyosarcoma patient-derived xenograft to examine precision medicine approaches and model acquired resistance.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 21 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We hypothesize that gene expression in the CS-exposed lungs of this strain (A/J) of mice would be able to give clues about the molecular mechanism of emphysema development, thus contributing to this phenotype. More specifically, although imbalance in oxidants/antioxidants and proteinase/antiproteinase pathways drives the pathogenesis of COPD, the molecular mechanisms involved in the development of emphysema are poorly understood. In order to test this hypothesis at the gene expression level, we utilized microarray analysis to examine transcriptional differences between CS-exposed and Air-exposed groups of mice.
Publication Title
Cigarette smoke-induced emphysema in A/J mice is associated with pulmonary oxidative stress, apoptosis of lung cells, and global alterations in gene expression.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We hypothesize that gene expression in the cigarette smoke (CS) exposed neonatal lung and age-matched controls will be divergent. CS exposed lung will have divergence of immune response genes and structural genes. The lungs of (6) 2 week old neonatal mice exposed to 2 weeks of CS were compared to the lung of (4) 2 week old age-matched control mice. We utilized microarray analysis to examine transcriptional differences between smoke exposed neonatal lung and age-matched controls.
Publication Title
Impaired lung homeostasis in neonatal mice exposed to cigarette smoke.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This experiment was conducted to test multiple hypotheses: 1) long-wave 365 nm UV light exposure at low fluences does not alter gene expression of hMSC, 2) presence of radical species during polymerization causes DNA damage in hMSC, 3) 3D encapsulation of hMSC causes changes in gene expression of hMSC compared with traditional 2D culture, 4) Differencesin 3D hydrogel networks induce gene expression changes in hMSC
Publication Title
Low-Dose, Long-Wave UV Light Does Not Affect Gene Expression of Human Mesenchymal Stem Cells.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 11 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Three groups of male +b and bb rats were obtained (ages between 6 and 14 months) and intestinal scrapes were taken. Tissues was combined from 3 rats per group and processed for gene chip analysis.
Publication Title
Induction of arachidonate 12-lipoxygenase (Alox15) in intestine of iron-deficient rats correlates with the production of biologically active lipid mediators.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To study effects of IFNalpha treatment on monocyte-derived macrophages which may influence susceptibility or resistance to HIV.
Publication Title
Interleukin-27 inhibition of HIV-1 involves an intermediate induction of type I interferon.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
Description
To investigate the role of RAD21 in the transcriptional regulation of global gene expression at early stage of colorectal cancer developments, we peformed the genome-wide analysis to map genomic regions bound by Rad21 in normal small testinal crypts and tumors (adenomas) harvested from Apc Min/+ mice using ChIP-seq. ChIP-seq naalysis identified high confidence RAD21 binding sites unique to normal crypts or adenomas, as well as those common to both tissues. We further performed RNA-seq to profile the changes in gene expression from normal WT crypts to adenomas at the very early stage of adenomagenesis in the context of Rad21 heterozygous loss. Overall design: mRNA profiles of normal small intestinal crypts (WT) and adenomas from Apc Min/+ and Apc Min/+:Rad21+/- double mutant mouse; Mapping of Rad21 genomic binding sites in normal intestinal crypts (WT) and Apc Min/+ adenomas
Publication Title
Cohesin Rad21 mediates loss of heterozygosity and is upregulated via Wnt promoting transcriptional dysregulation in gastrointestinal tumors.
Sample Metadata Fields
No sample metadata fields
View Samples