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GSE6613
Homo sapiens
105 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Parkinsons disease (PD) progresses relentlessly and affects five million people worldwide. Laboratory tests for PD are critically needed for developing treatments designed to slow or prevent progression of the disease. We performed a transcriptome-wide scan in 105 individuals to interrogate the molecular processes perturbed in cellular blood of patients with early-stage PD. The molecular marker here identified is strongly associated with risk of PD in 66 samples of the training set (third tertile cross-validated odds ratio of 5.7 {P for trend 0.005}). It is further validated in 39 independent test samples (third tertile odds ratio of 5.1 {P for trend 0.04}). The genes differentially expressed in patients with PD, or Alzheimers or progressive supranuclear palsy offer unique insights into disease-linked processes detectable in peripheral blood. Combining gene expression scans in blood and linked clinical data will facilitate the rapid characterization of candidate biomarkers as demonstrated here with respect to PD.
Publication Title
Molecular markers of early Parkinson's disease based on gene expression in blood.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 23 Downloadable Samples
Illumina HiSeq 2000
Description
Human lung adenocarcinoma exhibits a propensity for de-differentiation, which complicates diagnosis and treatment, and predicts for poor overall patient survival. In genetically engineered mouse (GEM) models of lung cancer, expression of the BRAFV600E oncoprotein kinase initiates the growth of benign tumors that retain characteristics of their cell of origin, alveolar type II (ATII) pneumocytes. Cooperating genetic alterations such as silencing of the PTEN tumor suppressor or expression of mutationally-activated PI3-kinase-a (PIK3CAH1047R) promote malignant progression of such benign tumors to malignant adenocarcinoma, though their effects on differentiation status are unknown. To address this in vivo, we generated a new conditional BrafCAT allele in which Cre-mediated recombination leads to expression of a bi-cistronic mRNA encoding both BRAFV600E and the tdTomato fluorescent protein. Using this model, we demonstrate that coincident expression of BRAFV600E and PIK3CAH1047R in ATII pneumocytes leads to rapid and widespread cell de-differentiation. Surprisingly, the combined effects of BRAFV600E and PIK3CAH1047R on ATII pneumocyte identity occurred without loss of expression of the lung lineage transcription factors NKX2.1, FOXA1, or FOXA2. Instead, we demonstrate a novel role of PGC1a in maintaining pneumocyte identity, which is lost upon PIK3CAH1047R expression. These findings provide additional insight into how two of the most commonly mutated growth factor signaling pathways contribute to the pathogenesis of lung adenocarcinoma. Overall design: BRAFV600E mutant mouse lung adenocarcinoma (n=6) vs BRAFV600E;PIK3CAH1047R mutant lung adenocarcinoma (n= 8), and BRAFV600E;PGC1aHET (n=5) vs BRAFV600E;PGC1aNULL tumors (n=4)
Publication Title
Mutationally-activated PI3'-kinase-α promotes de-differentiation of lung tumors initiated by the BRAF<sup>V600E</sup> oncoprotein kinase.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
To accelerate the development of disease-modifying therapeutics for Huntingtons disease (HD), a dynamic biomarker of disease activity and treatment response is critically needed.
Publication Title
Transcriptional modulator H2A histone family, member Y (H2AFY) marks Huntington disease activity in man and mouse.
Sample Metadata Fields
Sex, Specimen part
View Samples- Caenorhabditis elegans
- 51 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
DAF-16/FOXO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage.
Sample Metadata Fields
Treatment
View Samples- Caenorhabditis elegans
- 36 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Genome maintenance defects cause complex disease phenotypes characterized by developmental failure, cancer susceptibility and premature aging. It remains poorly understood how DNA damage responses function during organismal development and maintain tissue functionality when DNA damage accumulates with aging. Here we show that the FoxO transcription factor DAF-16 is activated in response to DNA damage during development while the DNA damage responsiveness of DAF-16 declines with aging. We find that in contrast to its established role in mediating starvation arrest, DAF-16 alleviates DNA damage induced developmental arrest and even in the absence of DNA repair promotes developmental growth and enhances somatic tissue functionality. We demonstrate that the GATA transcription factor EGL-27 co-regulates DAF-16 target genes in response to DNA damage and together with DAF-16 promotes developmental growth. We propose that EGL-27/GATA activity specifies DAF-16 mediated DNA damage responses to enable developmental progression and to prolong tissue functioning when DNA damage persists.
Publication Title
DAF-16/FOXO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage.
Sample Metadata Fields
Treatment
View Samples- Caenorhabditis elegans
- 15 Downloadable Samples
Affymetrix C. elegans Genome Array (celegans)
Description
Genome maintenance defects cause complex disease phenotypes characterized by developmental failure, cancer susceptibility and premature aging. It remains poorly understood how DNA damage responses function during organismal development and maintain tissue functionality when DNA damage accumulates with aging. Here we show that the FoxO transcription factor DAF-16 is activated in response to DNA damage during development while the DNA damage responsiveness of DAF-16 declines with aging. We find that in contrast to its established role in mediating starvation arrest, DAF-16 alleviates DNA damage induced developmental arrest and even in the absence of DNA repair promotes developmental growth and enhances somatic tissue functionality. We demonstrate that the GATA transcription factor EGL-27 co-regulates DAF-16 target genes in response to DNA damage and together with DAF-16 promotes developmental growth. We propose that EGL-27/GATA activity specifies DAF-16 mediated DNA damage responses to enable developmental progression and to prolong tissue functioning when DNA damage persists.
Publication Title
DAF-16/FOXO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We analyzed gene expression profiles of IL-18 generated murine NK cells in comparison to unstimulated, freshly isolated splenic NK cells.
Publication Title
Immunoregulatory natural killer cells suppress autoimmunity by down-regulating antigen-specific CD8+ T cells in mice.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Drosophila melanogaster
- 8 Downloadable Samples
- Illumina Genome Analyzer IIx, Illumina HiSeq 2000
Description
mRNA sequencing was used to identify genome wide transcriptional changes occuring in fly heads in response to spermidine feeding. This study shed light on the molecular mechanisms through wich spermidine can protect against age-dependent memory impairment. Overall design: mRNA profiles from 3 and 10 day old Drosophila melanogaster heads were generated in duplicate by deep sequencing using Illumina GAIIx. mRNA profiles from flies that were fed food with 5mM spermidine were compared to profiles from flies that had no spermidine in thier food.
Publication Title
Restoring polyamines protects from age-induced memory impairment in an autophagy-dependent manner.
Sample Metadata Fields
Age, Specimen part, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Uniparental parthenotes are considered an unwanted byproduct of in vitro fertilization. In utero parthenote development is severely compromised by defective organogenesis and in particular by defective cardiogenesis. Although developmentally compromised, apparently pluripotent stem cells can be derived from parthenogenetic blastocysts. Here we hypothesized that nonembryonic parthenogenetic stem cells (PSCs) can be directed toward the cardiac lineage and applied to tissue-engineered heart repair. We first confirmed similar fundamental properties in murine PSCs and embryonic stem cells (ESCs), despite notable differences in genetic (allelic variability) and epigenetic (differential imprinting) characteristics. Haploidentity of major histocompatibility complexes (MHCs) in PSCs is particularly attractive for allogeneic cell-based therapies. Accordingly, we confirmed acceptance of PSCs in MHC-matched allotransplantation. Cardiomyocyte derivation from PSCs and ESCs was equally effective. The use of cardiomyocyte-restricted GFP enabled cell sorting and documentation of advanced structural and functional maturation in vitro and in vivo. This included seamless electrical integration of PSC-derived cardiomyocytes into recipient myocardium. Finally, we enriched cardiomyocytes to facilitate engineering of force-generating myocardium and demonstrated the utility of this technique in enhancing regional myocardial function after myocardial infarction. Collectively, our data demonstrate pluripotency, with unrestricted cardiogenicity in PSCs, and introduce this unique cell type as an attractive source for tissue-engineered heart repair.
Publication Title
Parthenogenetic stem cells for tissue-engineered heart repair.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The right ventricle (RV) differs in several aspects from the left ventricle (LV) including its embryonic origin, physiological role and anatomical design. In contrast to LV hypertrophy, little is known about the molecular circuits, which are activated upon RV hypertrophy (RVH). We established a highly reproducible model of RVH in mice using pulmonary artery clipping (PAC), which avoids detrimental RV pressure overload and thus allows long-term survival of operated mice. Magnetic resonance imaging revealed pathognomonic changes with striking similarities to human congenital heart disease- or pulmonary arterial hypertension- patients. Comparative, microarray based transcriptome analysis of right- and left-ventricular remodeling identified distinct transcriptional responses to pressure-induced hypertrophy of either ventricle, which were mainly characterized by stronger transcriptional responses of the RV compared to the LV myocardium. Hierarchic cluster analysis revealed a RV- and LV-specific pattern of gene activity after induction of hypertrophy, however, we did not find evidence for qualitatively distinct regulatory pathways in RV compared to LV. Data mining of nearly three thousand RV-enriched genes under PAC disclosed novel potential (co)-regulators of long-term RV remodeling and hypertrophy. We reason that specific inhibitory mechanisms in RV restrict excessive myocardial hypertrophy and thereby contribute to its vulnerability to pressure overload.
Publication Title
Identification of right heart-enriched genes in a murine model of chronic outflow tract obstruction.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples