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GSE112681
Homo sapiens
1117 Downloadable Samples
Illumina HumanHT-12 V3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Whole blood transcriptome analysis in amyotrophic lateral sclerosis: A biomarker study.
Sample Metadata Fields
Sex, Disease
View Samples- Homo sapiens
- 741 Downloadable Samples
Illumina HumanHT-12 V3.0 expression beadchip
Description
Transcriptome-wide analysis of whole blood gene expression profiles of ALS patients, gender- and age-matched controls and patients diagnosed with diseases mimicking ALS at a tertiary referral center for motor neuron diseases.
Publication Title
Whole blood transcriptome analysis in amyotrophic lateral sclerosis: A biomarker study.
Sample Metadata Fields
Sex, Disease
View Samples- Homo sapiens
- 376 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Transcriptome-wide analysis of whole blood gene expression profiles of ALS patients, gender- and age-matched controls and patients diagnosed with diseases mimicking ALS at a tertiary referral center for motor neuron diseases.
Publication Title
Whole blood transcriptome analysis in amyotrophic lateral sclerosis: A biomarker study.
Sample Metadata Fields
Sex, Disease
View Samples- Homo sapiens
- 70 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), Affymetrix Human Full Length HuGeneFL Array (hu6800)
Description
Lectins are proteins present on cell surfaces or as shed extracellular proteins that function in innate immune defense as phagocytic receptors to recognize specific bacterial cell wall components. Based on the knowledge that cigarette smoking is associated with increased risk of bacterial infection, we hypothesized that cigarette smoking may modulate the expression of lectin genes in the airway epithelium. Affymetrix HG U133 Plus 2.0 microarrays were used to survey expression of lectin genes in large (3rd to 4th order bronchi) airway epithelium from 9 normal nonsmokers and 20 phenotypic normal smokers and small (10th to 12th order bronchi) airway epithelium from 13 normal nonsmokers and 20 phenotypic normal smokers. From the 72 lectin genes that were surveyed, there were no changes (>2-fold change, p<0.05) in gene expression in either large or small airway epithelium among normal smokers compared to nonsmokers except for a striking down regulation in both large and small airway epithelium of normal smokers of intelectin 1, a recently described lectin that participates in the innate immune response by recognizing and binding to galactofuranosyl residues in the cell walls of bacteria (large airway epithelium, p<0.003; small airway epithelium, p<0.002). TaqMan RT-PCR confirmed the observation that intelectin 1 was down-regulated in both large (p<0.05) and small airway epithelium (p<0.02) of normal smokers compared to normal nonsmokers. Immunohistochemistry assessment of biopsies of the large airway epithelium of normal nonsmokers demonstrated intelectin 1 was expressed in secretory cells, with qualitatively decreased expression in biopsies from normal smokers. Western analysis confirmed the decreased expression of intelectin 1 in airway epithelium of normal smokers compared to normal nonsmokers (p<0.02). Finally, compared to normal nonsmokers, intelectin 1 expression was decreased in small airway epithelium of smokers with early COPD (n= 13, p<0.001) and smokers with established COPD (n= 14, p<0.001), in a fashion similar to that of normal smokers. In the context that intelectin 1 is an epithelial molecule that likely plays a role in defense against bacteria, the down regulation of expression of intelectin 1 in response to cigarette smoking may contribute to the increase in susceptibility to infections observed in smokers, including those with COPD.
Publication Title
Decreased expression of intelectin 1 in the human airway epithelium of smokers compared to nonsmokers.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 12 Downloadable Samples
IlluminaHiSeq2500
Description
High uniform fluid shear stress (FSS) is atheroprotective and preserves the endothelial phenotype and function through activation of downstream mediators such as MAPK7 (Erk5). Endothelial cells respond to FSS thanks to mechanotransduction. However, how the resulting signaling is integrated and resolved at the epigenetic level, remains elusive. We hypothesized that Polycomb methyltransferase EZH2 is involved in the effects of FSS in human endothelial cells. We showed that FSS decreases the expression of the Polycomb methyltransferase EZH2. Despite simultaneous activation of MAPK7, MAPK7 pathway does not directly influence the transcription of EZH2. Interestingly though, the knock down of EZH2 activates the protective MAPK7 signaling in endothelial cells, even in the absence of FSS. To understand the influence of the FSS-decreased expression of EZH2 on endothelial transcriptome, we performed RNA-seq and differential gene expression analysis. We identified candidate groups of genes dependent on both EZH2 and FSS. Among those, Gene Ontology overrepresentation analysis revealed highly significant enrichment of the cell cycle-related genes, suggesting changes in proliferation. Indeed, the depletion of EZH2 strongly inhibited endothelial proliferation, indicating cell cycle arrest. The concomitant decrease in CCNA expression suggests the transition of endothelial cells into a quiescent phenotype. Further bioinformatical analysis suggested TXNIP as a possible mediator between EZH2 and cell cycle-related gene network. Our data show that EZH2 is a FSS-responsive gene. Decreased EZH2 levels enhance the activation of the atheroprotective MAPK7 signaling. Decrease in EZH2 under FSS mediates the decrease in the expression of the network of cell cycle-related genes, which allows the cells to enter quiescence. EZH2 is therefore important for the protective effects of FSS in endothelium. Overall design: Puromycin-selected HUVEC (Human Umbilical Vein Endothelial Cells, Lonza, Switzerland) cells, expressing either scrambled control (SCR) or anti-EZH2 short-hairpin (shEZH2) constructs (at total 7 days after the first viral transduction), were used in FSS experiments (72h of control static culture or exposure to 20 dynes/cm2 of fluid shear stress, using Ibidi pump system (in µ-Slides I 0.4 Luer, Ibidi, Planegg/Martinsried, Germany)). Each replicate experiment consisted of viral transductions and puromycin selection of a separate HUVEC batch, followed by the FSS experiment. Two FSS experimental sets of the same HUVEC batch were run every time in parallel and lysed at the same end time point, one in RNAse-free conditions with RNA-Easy Mini Plus kit RLT Plus lysis buffer (QIAGEN, Venlo, The Netherlands), and one with RIPA buffer. The RIPA-lysates were analyzed with Western blotting and confirmed the complete (no protein present) knock-down of EZH2. From the RNA-lysates, RNA was isolated using the RNA-Easy Mini Plus kit (QIAGEN, Venlo, The Netherlands). High quality RNA samples (pre-assessed by Nanodrop measurements) were further processed in the Genome Analysis Facility of the University Medical Center Groningen. The RNA quality and integrity were verified using PerkinElmer Labchip GX with a cut-off value of 9 (scale 1 to 10, where 9 is very high quality RNA). RNA library was created in accordance with the TruSeqTM RNA Sample Preparation v2 Guide (Illumina, San Diego, CA, USA), using the PerkinElmer Sciclone liquid handler, resulting in 330bp cDNA fragments. The paired-end sequencing (100bp reads) was performed using the Illumina HiSeqTM 2500. (Quoted from the Materials and Methods of the related manuscript, with adjustments).
Publication Title
The decrease in histone methyltransferase EZH2 in response to fluid shear stress alters endothelial gene expression and promotes quiescence.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 32 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Fanconi anemia (FA) is a rare inherited disease complicated by aplastic anemia. There is evidence that hematopoietic stem cells have lost self replicative capacity and undergo apoptosis when exposed to inhibitory cytokines including interferon gamma and tumor necrosis factor-alpha.
Publication Title
TLR8-dependent TNF-(alpha) overexpression in Fanconi anemia group C cells.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Mononuclear phagocytes play an important role in the removal of apoptotic cells by expressing cell surface receptors that recognize and remove apoptotic cells. Based on the knowledge that cigarette smoking is associated with increased lung cell turnover, we hypothesized that alveolar macrophages (AM) of normal cigarette smokers may exhibit enhanced expression of apoptotic cell removal receptor genes. AM obtained by bronchoalveolar lavage of normal non-smokers (n=11) and phenotypic normal smokers (n=13, 36 6 pack-yr) were screened for mRNA expression of all known apoptotic cell removal receptors using Affymetrix HG-U133 Plus 2.0 chips with TaqMan RT-PCR confirmation. Of the 14 known apoptotic receptors expressed, only MER Tyrosine Kinase (MERTK), a transmembrane tyrosine kinase receptor, was significantly up-regulated in smokers. MERTK expression was then assessed in AM of smokers vs nonsmokers by TaqMan RT-PCR, immunohistochemistry, Western and flow analysis. Smoker AM had up-regulation of MERTK mRNA levels (smoker vs non-smoker, 3.6-fold by microarray, p<0.003; 9.5-fold by TaqMan RT-PCR, p<0.02). Immunohistochemistry demonstrated a qualitative increase in MERTK protein expression on AM of smokers. Increased protein expression of MERTK on AM of smokers was confirmed by Western and flow analyses (p< 0.007 and p< 0.0002, respectively). MERTK, a cell surface receptor that recognizes apoptotic cells, is expressed on human AM, and its expression is up-regulated in AM of cigarette smokers. This may reflect an increased demand for removal of apoptotic cells in smokers, an observation with implications for the development of chronic obstructive pulmonary disease (COPD), a disorder associated with dysregulated apoptosis of lung parenchymal cells.
Publication Title
Overexpression of apoptotic cell removal receptor MERTK in alveolar macrophages of cigarette smokers.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Hematopoietic cells arise from spatiotemporally restricted domains in the developing embryo. Although studies of non-mammalian animal and in vitro embryonic stem cell models suggest a close relationship among cardiac, endocardial, and hematopoietic lineages, it remains unknown whether the mammalian heart tube serves as a hemogenic organ akin to the dorsal aorta. Here, we examined the hemogenic activity of the developing endocardium. Mouse heart explants generated myeloid and erythroid colonies in the absence of circulation. Hemogenic activity arose from a subset of endocardial cells in the outflow cushion and atria earlier than in the aorta-gonad-mesonephros region, and was transient and definitive in nature. Interestingly, key cardiac transcription factors, Nkx2-5 and Isl1, were expressed in and required for the hemogenic activity of the endocardium. Together, these data suggest that a subset of endocardial and yolk sac endothelial cells expressing cardiac markers serve as a de novo source for transient definitive hematopoietic progenitors.
Publication Title
Haemogenic endocardium contributes to transient definitive haematopoiesis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 50 Downloadable Samples
- Illumina HiSeq 2500
Description
This study examines the global transcriptomic profiles in peripheral blood of Papua New Guinea newborns at birth (D0) comparing with follow up at day 1 (D1), day 3 (D3), or day 7 (D7) post birth. Overall design: Systems biology provides a powerful approach to unravel complex biological processes yet it has not been applied systematically to samples from newborns, a group highly vulnerable to a wide range of diseases. Published methods rely on blood volumes that are not feasible to obtain from newborns. We optimized methods to extract transcriptomic, proteomic, metabolomic, cytokine/chemokine, and single cell immune phenotyping data from <1ml of blood, a volume readily obtained from newborns. Furthermore, indexing to baseline and applying innovative integrative computational methods that address the challenge of few data points with many features enabled identification of robust findings within a readily achievable sample size. This approach uncovered dramatic changes along a stable developmental trajectory over the first week of life. The ability to extract information from 'big data' and draw key insights from such small sample volumes will enable and accelerate characterization of the molecular ontogeny driving this crucial developmental period.
Publication Title
Dynamic molecular changes during the first week of human life follow a robust developmental trajectory.
Sample Metadata Fields
Sex, Subject
View Samples- Saccharomyces cerevisiae
- 30 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
The Rad23/Rad4 protein complex plays a major role in DNA damage recognition during nucleotide excision repair (NER) in yeast. We recently showed that two distinct pathways contribute to efficient NER in yeast. The first operates independently of de novo protein synthesis and requires a nonproteolytic function of the 19S regulatory complex of the 26S proteasome and Rad23. The second pathway requires de novo protein synthesis, and relies on the activity of a newly identified Rad7-containing E3 ubiquitin ligase that ubiquitinates Rad4 in response to UV. Surprisingly, we found that cells deleted of either Rad23 or Rad4 caused reduced Rad4 and Rad23 mRNA levels respectively. We considered the possibility of an unexpected role of Rad23 and Rad4 in regulating the expression of genes involved in the transcriptional response to DNA damage. Gene expression profiling has suggested that Rad23 and Rad4 may function as a complex to affect transcription of a small subset of genes in response to UV damage. To determine how Rad4 and Rad23 contribute to the regulation of these genes, we have examined the occupancy of Rad4/Rad23 in their promoter regions by chromatin immunoprecipitation (ChIP), both in the presence and absence of UV damage. Our preliminary ChIP data suggests that the Rad4/Rad23 complex regulates a set of genes in response to UV light. We also proposed that the transcriptional regulatory activity of the Rad4-Rad23 complex required Rad4 ubiquitination. These arrays test this theory using the psocs mutant strain, which is unable to facilitate Rad4 ubiquitination after UV irradiation.
Publication Title
UV induced ubiquitination of the yeast Rad4-Rad23 complex promotes survival by regulating cellular dNTP pools.
Sample Metadata Fields
Time
View Samples