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GSE26350
Rattus norvegicus
72 Downloadable Samples
Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Retrograde signaling from axon to soma activates intrinsic regeneration mechanisms in lesioned peripheral sensory neurons; however, the links between axonal injury signaling and the cell body response are not well understood. Here, we used phosphoproteomics and microarrays to implicate ~900 phosphoproteins in retrograde injury signaling in rat sciatic nerve axons in vivo and ~4500 transcripts in the in vivo response to injury in the dorsal root ganglia. Computational analyses of these data sets identified ~400 redundant axonal signaling networks connected to 39 transcription factors implicated in the sensory neuron response to axonal injury. Experimental perturbation of individual overrepresented signaling hub proteins, including Abl, AKT, p38, and protein kinase C, affected neurite outgrowth in sensory neurons. Paradoxically, however, combined perturbation of Abl together with other hub proteins had a reduced effect relative to perturbation of individual proteins. Our data indicate that nerve injury responses are controlled by multiple regulatory components, and suggest that network redundancies provide robustness to the injury response
Publication Title
Signaling to transcription networks in the neuronal retrograde injury response.
Sample Metadata Fields
No sample metadata fields
View Samples- Sus scrofa
- 24 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
This study aimed to characterize differences in gene expression in piglets inoculated with porcine circovirus type 2 (PCV2), the essential causative agent of postweaning multisystemic wasting syndrome (PMWS). Comparisons between control and PCV2-inoculated pigs were done at five different time points: 1, 2, 5, 8, and 29 days post-inoculation.
Publication Title
Time course differential gene expression in response to porcine circovirus type 2 subclinical infection.
Sample Metadata Fields
Age, Specimen part
View Samples- Sus scrofa
- 25 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
Postweaning multisystemic wasting syndrome (PMWS) is one of the pig diseases with major economic impact worldwide. Clinical, pathologic and some immunologic aspects of this disease are well-known, but the molecular mechanisms underlying pathogenic mechanisms of the disease are still poorly understood. The objective of the present study was to investigate the global changes in gene expression in the mediastinal lymph nodes from pigs naturally affected by PMWS and healthy counterparts, using the Affymetrix Porcine Genechip. This is the first study on gene expression in pigs naturally affected by PMWS. The present results allowed identifying potential mechanisms underlying the inflammation, lymphocyte depletion in lymphoid tissues and immune suppression, which are key features of PMWS.
Publication Title
Microarray analysis of mediastinal lymph node of pigs naturally affected by postweaning multisystemic wasting syndrome.
Sample Metadata Fields
Age, Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 55 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Catechol-O-methyltransferase (COMT) is an ubiquitously expressed enzyme that maintains basic biologic functions by inactivating catechol substrates. In humans, polymorphic variance at the COMT locus has been associated with modulation of pain sensitivity (Andersen & Skorpen, 2009) and risk for developing psychiatric disorders (Harrison & Tunbridge, 2008). A functional haplotype associated with increased pain sensitivity was shown to result in decreased COMT activity by altering mRNA secondary structure-dependent protein translation (Nackley et al., 2006). However, the exact mechanisms whereby COMT modulates pain sensitivity and behavior remain unclear and can be further studied in animal models. We have pursued a genome-wide approach to examining gene expression in multiple brain regions in inbred strains of mice and have discovered that Comt1 is differentially expressed. This expression difference was validated with qPCR. A B2-B4 Short Interspersed Element (SINE) was inserted in the 3'UTR of Comt1 in 14 strains that also shared a common haplotype. Experiments using mammalian expression vectors of full-length cDNA clones with and without the SINE element demonstrate that strains with the SINE haplotype (+SINE) have greater Comt1 enzymatic activity. +SINE mice also exhibit behavioral differences in anxiety assays and decreased pain sensitivity. These results suggest that a haplotype, defined by a 3'UTR B2-B4 SINE element, regulates Comt1 expression and mouse behavior.
Publication Title
Comt1 genotype and expression predicts anxiety and nociceptive sensitivity in inbred strains of mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Saccharomyces cerevisiae
- 37 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
We subjected yeast to two stresses, oxidative stress, which under current settings induces a fast and transient response in mRNA abundance, and DNA damage, which triggers a slow enduring response. Using microarrays, we performed a transcriptional arrest experiment to measure genome-wide mRNA decay profiles under each condition. Genome-wide decay kinetics in each condition were compared to decay experiments that were performed in a reference condition (only transcription inhibition without an additional stress) to quantify changes in mRNA stability in each condition. We found condition-specific changes in mRNA decay rates and coordination between mRNA production and degradation. In the transient response, most induced genes were surprisingly destabilized, while repressed genes were somewhat stabilized, exhibiting counteraction between production and degradation. This strategy can reconcile high steady-state level with short response time among induced genes. In contrast, the stress that induces the slow response displays the more expected behavior, whereby most induced genes are stabilized, and repressed genes destabilized. Our results show genome-wide interplay between mRNA production and degradation, and that alternative modes of such interplay determine the kinetics of the transcriptome in response to stress.
Publication Title
Transient transcriptional responses to stress are generated by opposing effects of mRNA production and degradation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We were interested to explain why p53 binds some high affinity sites in contrast to other high affinity sites that are not bound by p53.
Publication Title
p53 binds preferentially to genomic regions with high DNA-encoded nucleosome occupancy.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 9 Downloadable Samples
Illumina HiSeq 2500
Description
Mutations in the poly(A) ribonuclease (PARN) gene cause telomere diseases including familial idiopathic pulmonary fibrosis (IPF) and dyskeratosis congenita (DC)1,2, but how PARN deficiency impacts telomere maintenance is unclear. Here, using somatic cells and induced pluripotent stem (iPS) cells from DC patients with PARN mutations, we show that PARN is required for the 3' end maturation of the telomerase RNA component (TERC). Patient cells as well as immortalized cells in which PARN is disrupted show decreased levels of TERC. Deep sequencing of TERC RNA 3' termini reveals that PARN is required for removal of posttranscriptionally acquired oligo(A) tails that target nuclear RNAs for degradation. Diminished TERC levels and the increased oligo(A) forms of TERC are normalized by restoring PARN, which is limiting for TERC maturation in cells. Our results reveal a novel role for PARN in the biogenesis of TERC, and provide a mechanism linking PARN mutations to telomere diseases. Overall design: mRNA sequencing of fibroblasts, induced pluripotent stem cells, and 293 cell line.
Publication Title
Poly(A)-specific ribonuclease (PARN) mediates 3'-end maturation of the telomerase RNA component.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
The telomerase RNA component (TERC) is a critical determinant of cellular self renewal. Poly(A)-specific ribonuclease (PARN) is required for post-transcriptional maturation of TERC. PARN mutations lead to incomplete 3' end processing and increased destruction of nascent TERC RNA transcripts, resulting in telomerase deficiency and telomere diseases. Here, we determined that overexpression of TERC increased telomere length in PARN-deficient cells and hypothesized that decreasing post-transcriptional 3' oligo-adenylation of TERC would counteract the deleterious effects of PARN mutations. Inhibition of the noncanonical poly(A) polymerase PAP-associated domain–containing 5 (PAPD5) increased TERC levels in PARN-mutant patient cells. PAPD5 inhibition was also associated with increases in TERC stability, telomerase activity, and telomere elongation. Our results demonstrate that manipulating post-transcriptional regulatory pathways may be a potential strategy to reverse the molecular hallmarks of telomere disease. Overall design: mRNA sequencing of induced pluripotent stem cells and 293 cell line.
Publication Title
Posttranscriptional manipulation of TERC reverses molecular hallmarks of telomere disease.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
- Illumina HiSeq 2500
Description
Rationale. Lung inflammation in premature infants contributes to development of bronchopulmonary dysplasia (BPD), a chronic lung disease with long-term sequelae. Pilot studies administering budesonide suspended in surfactant have found reduced BPD without apparent adverse effects as occur with systemic dexamethasone therapy. Objectives. To determine effects of budesonide on differential genes expression in human fetal lung Overall design: Methods. We prepared RNA from 3 samples of human fetal lung at 23 weeks gestation before (preculture, PC) and after 4 days culture as explants with (Bud) or without (Way) budesonide (30 nM) and performed RNAseq on the 9 samples.
Publication Title
Antiinflammatory Effects of Budesonide in Human Fetal Lung.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Molecular characterization of the peripheral airway field of cancerization in lung adenocarcinoma.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples