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Saccharomyces cerevisiae
36 Downloadable Samples
Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
tRNAs are transcribed and partially processed in the nucleus before they are exported to the cytoplasm where they have an essential role in protein synthesis. Surprisingly, mature cytoplasmic tRNAs shuttle between nucleus and cytoplasm and its distribution is nutrient-dependent. At least three members of -importin family, Los1, Mtr10, and Msn5, function in tRNA nuclear-cytoplasmic intracellular movement. To test the hypothesis that the tRNA retrograde pathway regulates translation of particular transcripts
Publication Title
Genome-wide investigation of the role of the tRNA nuclear-cytoplasmic trafficking pathway in regulation of the yeast Saccharomyces cerevisiae transcriptome and proteome.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 35 Downloadable Samples
Illumina HiSeq 2500
Description
Retinopathy of prematurity (ROP) is the most common cause of childhood blindness worldwide and is caused by oxygen therapy necessary to prevent mortality after premature birth. We have previously demonstrated the efficacy of systemic hypoxia inducible factor (HIF) stabilization through HIF prolyl hydroxylase inhibition (HIF PHi) in protecting retinal vasculature from oxygen toxicity in a mouse model of ROP or oxygen induced retinopathy (OIR). We definitively demonstrated that hepatic HIF-1 can be activated to confer this protection using systemic dimethyloxalylglycine (DMOG) to prevent HIF-1a degradation. In this study we compare Roxadustat, a small molecule stabilizer of HIF-1 currently in phase 3 clinical trials for increasing erythropoiesis in adult patients with chronic kidney disease, to DMOG. We demonstrate that Roxadustat induces vascular protection during hyperoxia to induce the coordinated sequential growth of retinal vasculature with a 3-fold reduction in oxygen induced capillary loss (p-=0.001). In order to define the molecular mechanism of protection, we further compared the transcriptome of both liver and retina after systemic treatment with Roxadustat or DMOG. Similar gene expression profiles were identified in liver but very different effects on transcription were found in retinal tissues because Roxadustat, in contrast to DMOG, directly targets retina, confirmed by western blot and by rescue of the hepatic HIF-1 KO, two criteria that DMOG treatment is unable to fulfill. Systems pharmacologic analysis demonstrates that Roxadustat induces typical HIF regulated genes critical to aerobic glycolysis in liver and retinal tissues whereas DMOG, acting through either secreted hepatokines or by influence of systemic DMOG, downregulates cell adhesion/extracellular matrix interaction pathways while increasing expression of histone cluster genes. Stratification of liver transcriptomes to secreted gene products again shows close consensus of hepatic genes induced by both small molecules, and includes upregulation of a plethora of angiogenic proteins such as plasminogen activator inhibitor (PAI-1), erythropoietin (EPO), and orosomucosoid 2 (ORM2). Secondary validation of these transcripts by serum ELISA confirms secretion of EPO and PAI-1 into blood from liver. These findings definitively demonstrate that HIF stabilization can prevent OIR by two pathways: direct retinal HIF stabilization and induction of aerobic glycolysis or indirect, hepatic HIF-1 stabilization and increased serum angiokines. Systems pharmacology analysis therefore explains why intermittent, low dosage of small molecule HIF stabilizers creates a profound protective phenotype, because both pathways can take advantage of cytoprotection induced by the liver and by retina synergistically. These data provide a rationale for considering low dose, intermittent systemic administration of Roxadustat, currently in phase 3 trials in adults with chronic kidney disease, to eradicate ROP in children. Overall design: RNA-Seq of mice treated with PBS (control), DMOG, or Roxadustat from liver or retina.
Publication Title
Comparative systems pharmacology of HIF stabilization in the prevention of retinopathy of prematurity.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
GM-CSF controls the development of granulocytes but little is known about the contribution of the downstream mediating transcription factor STAT5A/B. To elucidate this pathway, we generated mice lacking the Stat5a and 5b genes in blood cells. Peripheral neutrophils were decreased and administration of 5-FU and GM-CSF failed to induce granulopoiesis in Stat5a/b-mutant mice. GMPs were isolated and cultured with GM-CSF. Both the number and size of STAT5A/B-null colonies were reduced and GM-CSF-induced survival of mature STAT5A/B-null neutrophils was impaired. Time-lapse cinematography and single cell tracking of GMPs revealed that STAT5A/B-null cells were characterized by a longer generation time and an increased cell death. Gene expression profiling experiments suggested that STAT5A/B directs GM-CSF signaling through the regulation of cell survival genes.
Publication Title
The transcription factors STAT5A/B regulate GM-CSF-mediated granulopoiesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
In this study, we explored the transcriptomic consequences of strong activation of the Notch pathway in embryonic human neural stem cells and in gliomas. For this we used a forced expression of the Notch intracellular domain (NICD).
Publication Title
Notch1 stimulation induces a vascularization switch with pericyte-like cell differentiation of glioblastoma stem cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples
GSE42498- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
In this study, we use a conditional mouse model for Cebpa to investigate the significance of C/EBP in HSCs. The frequency of HSCs is unaltered following deletion of C/EBP, however, upon serial transplantations of either full BM or purified HSCs, the stem cells and stem cell activity is lost. This is not due to increased proliferation, but rather caused by a shift from quiescence to apoptosis with a resultant exhaustion of the stem cell pool. We identify direct C/EBP target genes by combining genome-wide C/EBP ChIP-seq analysis in stem and progenitor cells with gene expression data from HSC with and without C/EBP. Furthermore, we explore the impact of C/EBP on active and repressive histone modifications by doing functional genome-wide ChIP-seq analysis of H3K4Me3 and H3K27Me3 in stem and progenitor cells with and without C/EBP.
Publication Title
C/EBPα is required for long-term self-renewal and lineage priming of hematopoietic stem cells and for the maintenance of epigenetic configurations in multipotent progenitors.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 52 Downloadable Samples
- Illumina HiSeq 2500
Description
Large numbers of ribonucleotides are incorporated into the eukaryotic nuclear genome during S-phase due to imperfect discrimination against ribonucleoside triphosphates by the replicative DNA polymerases. Ribonucleotides, by far the most common DNA lesion in replicating cells, destabilize the DNA, and an evolutionarily conserved DNA repair machinery, ribonucleotide excision repair (RER), ensures ribonucleotide removal. Complete lack of RER is embryonically lethal. Partial loss-of-function mutations in the genes encoding subunits of RNase H2, the enzyme essential for initiation of RER, cause the SLE-related type I interferonopathy Aicardi-Goutières syndrome. Here we establish that selective inactivation of RER in mouse epidermis results in spontaneous DNA damage, epidermal hyperproliferation associated with loss of hair follicle stem cells and hair follicle function. The animals develop keratinocyte intraepithelial neoplasia and invasive squamous cell carcinoma with complete penetrance, despite potent type I interferon production and skin inflammation. Compromised RER-mediated genome maintenance might represent an important tumor-promoting principle in human cancer. Overall design: CD45+ CD49f- cells were were isolated from skin cell suspensions by FACS. Total RNA was isolated using the RNeasy Micro Kit+ (Qiagen). mRNA libraries were prepared using a SMART protocol and subjected to deep sequencing on an Illumina®HiSeq 2500.
Publication Title
Ribonucleotide Excision Repair Is Essential to Prevent Squamous Cell Carcinoma of the Skin.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 2500
Description
Large numbers of ribonucleotides are incorporated into the eukaryotic nuclear genome during S-phase due to imperfect discrimination against ribonucleoside triphosphates by the replicative DNA polymerases. Ribonucleotides, by far the most common DNA lesion in replicating cells, destabilize the DNA, and an evolutionarily conserved DNA repair machinery, ribonucleotide excision repair (RER), ensures ribonucleotide removal. Complete lack of RER is embryonically lethal. Partial loss-of-function mutations in the genes encoding subunits of RNase H2, the enzyme essential for initiation of RER, cause the SLE-related type I interferonopathy Aicardi-Goutières syndrome. Here we establish that selective inactivation of RER in mouse epidermis results in spontaneous DNA damage, epidermal hyperproliferation associated with loss of hair follicle stem cells and hair follicle function. The animals develop keratinocyte intraepithelial neoplasia and invasive squamous cell carcinoma with complete penetrance, despite potent type I interferon production and skin inflammation. Compromised RER-mediated genome maintenance might represent an important tumor-promoting principle in human cancer. Overall design: Keratinocytes (CD49f+) cells were isolated from skin cell suspensions by FACS. Total RNA was isolated using the RNeasy Mini Kit+ (Qiagen). mRNA libraries were prepared and subjected to deep sequencing on an Illumina®HiSeq.
Publication Title
Ribonucleotide Excision Repair Is Essential to Prevent Squamous Cell Carcinoma of the Skin.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The human hair follicle bulge is an important niche for keratinocyte stem cells (KSC). Elucidation of human bulge cell biology could be facilitated by analysis of global gene expression profiles and identification of unique cell surface markers. The lack of distinctive bulge morphology in human hair follicles has hampered studies of bulge cells and KSC. In this study, we determined the distribution of label-retaining cells to carefully define the human anagen bulge. Using navigated-laser capture microdissection, bulge cells and outer root sheath cells from other follicle regions were obtained and analyzed with cDNA microarrays. Gene transcripts encoding inhibitors of WNT and Activin/BMP signaling were over-represented in the bulge while genes responsible for cell proliferation were under-represented, consistent with quiescent non-cycling KSC in anagen follicles. Positive markers for bulge cells included CD200, PHLDA1, follistatin, and frizzled homolog 1 while CD24, 34, 71 and 146 were preferentially expressed by non-bulge keratinocytes. Importantly, CD200+ cells (CD200hi24lo34lo71lo146lo) obtained from hair follicle suspensions demonstrated high colony forming efficiency in clonogenic assays, indicating successful enrichment of living human bulge stem cells.
Publication Title
Characterization and isolation of stem cell-enriched human hair follicle bulge cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
We used microarray analysis to identify differences in gene expression levels in heart following an 18h (overnight) fast in WT control and KLF15-null mice
Publication Title
Kruppel-like factor 15 is a critical regulator of cardiac lipid metabolism.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 77 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Epstein-Barr virus-associated primary nodal T/NK-cell lymphoma shows a distinct molecular signature and copy number changes.
Sample Metadata Fields
Disease, Disease stage
View Samples