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GSE76985
Saccharomyces cerevisiae
4 Downloadable Samples
Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
KP1019 (trans-[tetrachlorobis(1H-indazole) ruthenate(III)]) is a ruthenium complex that exhibited anti-cancer activity in several in vitro and in vivo studies. KP1019 was even efficient against cancer cells that were resistant to other chemotherapeutic agents and thus emerged as a promising anti-cancer drug without dose-limiting cytotoxicity. However, the molecular mechanisms of its action are elusive.
Publication Title
A systematic assessment of chemical, genetic, and epigenetic factors influencing the activity of anticancer drug KP1019 (FFC14A).
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Purpose: Klf5 plays a critical role in the mouse ocular surface (Kenchegowda et al., 2011. Dev Biol. 356:5-18). Here, we compare wild-type (WT) and Klf5-conditional null (Klf5CN) corneal gene expression at postnatal day-11 (PN11) and PN56 to identify the Klf5-target genes. Methods: Gene expression was compared using Affymetrix microarrays with QPCR validation. Transient transfection assays examined the effect of Klf5 on selected target gene promoter activities. Whole-mount corneal immunofluorescent staining examined neovascularization and CD45+ macrophage influx. Results: Expression of 714 and 753 genes was increased, and 299 and 210 genes decreased in PN11 and PN56 Klf5CN corneas, respectively, with 366 concordant increases, 72 concordant decreases and 3 discordant changes. Canonical pathway analysis identified 35 and 34 significantly (p<0.001) enriched pathways at PN11 and PN56, respectively, with 24 common pathways. PN56 Klf5CN corneas shared 327 increases and 91 decreases with the previously described Klf4CN corneas (Swamynathan et al., 2008. IOVS 49:3360-70). Angiogenesis and immune response-related genes were affected consistent with lymphangiogenesis and macrophage influx in Klf5CN corneas, respectively. Expression of 1574 genes was increased and 1915 decreased, in the WT PN56 compared with PN11 corneas. Expression of many collagens, matrix metalloproteinases and other extracellular matrix associated genes decreased in WT corneas between PN11 and PN56, while that of solute carrier family members increased. Conclusions: Differences in PN11 and PN56 corneal Klf5-target genes reveal dynamic changes in Klf5 functions during corneal maturation. Klf4- and Klf5-target genes do not overlap, consistent with their non-redundant roles in the mouse cornea.
Publication Title
Critical role of Klf5 in regulating gene expression during post-eyelid opening maturation of mouse corneas.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Conditional disruption of Klf4 in the ectoderm-derived tissues of the eye results in defective cornea, conjunctiva and the lens.
Publication Title
Regulation of mouse lens maturation and gene expression by Krüppel-like factor 4.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 33 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Ficolled AML-M0 sample gene expression profiles on Affymetrix HGU133Plus2.0 GeneChips. Acute myeloid leukemia (AML) classified as FAB-M0 is defined as a subtype with minimally differentiated morphology. Here we investigated by gene expression (GEP) profiling whether AML-M0 cases should be considered as one or more unique molecular subgroups that discriminates them from other AML patients. By applying GEP and subsequent unsupervised analysis of 35 AML-M0 samples and 253 previously reported AML cases, we demonstrate that AML-M0 cases express a unique signature. Hematological transcription regulators such as CEBPA, CEBPD, PU.1 and ETV6 and the differentiation associated gene MPO appeared strongly down-regulated, in line with the very primitive state of this type of leukemia. Moreover, AML M0 cases appeared to have a strong positive correlation with a previously defined immature AML subgroup with adverse prognosis. AML-M0 leukemias frequently carry loss-of-function RUNX-1 mutation and unsupervised analyses revealed a striking distinction between cases with and without mutations. RUNX1 mutant AML-M0 samples showed a distinct up-regulation of B-cell-related genes, e.g. members of the B-cell receptor complex, transcriptions regulators RUNX3, ETS2, IRF8 or PRDM1 and major histocompatibility complex class II genes. Importantly, expression of one single gene, i.e. BLNK, enabled prediction of RUNX1 mutations in AML-M0 with high accuracy. We propose that RUNX1 mutations in this subgroup of AML cause lineage infidelity, leading to aberrant co-expression of myeloid and B-lymphoid genes in the same cells.
Publication Title
Gene expression profiling of minimally differentiated acute myeloid leukemia: M0 is a distinct entity subdivided by RUNX1 mutation status.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Thyroid hormone is crucial for normal brain development. Thyroid hormone transporters control thyroid hormone homeostatis in brain. Mutations in the thyroid hormone transporter MCT8 result in a complex endocrine and neurological phenotype.
Publication Title
Transcriptional profiling of fibroblasts from patients with mutations in MCT8 and comparative analysis with the human brain transcriptome.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
Illumina HiSeq 2500
Description
We discuss the use of pluripotent stem cell lines carrying fluorescent reporters driven by retinal promoters to derive three-dimensional (3-D) retina in culture and how this system can be exploited for elucidating human retinal biology, creating disease models in a dish, and designing targeted drug screens for retinal and macular degeneration. Furthermore, we realize that stem cell investigations are labor-intensive and require extensive resources. To expedite scientific discovery by sharing of resources and to avoid duplication of efforts, we propose the formation of a Retinal Stem Cell Consortium. In the field of vision, such collaborative approaches have been enormously successful in elucidating genetic susceptibility associated with age-related macular degeneration. Overall design: CRX+ flow sorted cells from human retina derived organoids were collected at 6 time points during differentiation (day (D) 37, 48, 67, 90, 134, 220).
Publication Title
Treatment Paradigms for Retinal and Macular Diseases Using 3-D Retina Cultures Derived From Human Reporter Pluripotent Stem Cell Lines.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 58 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Clinical remission is apparent when laboratory markers of inflammation are normal and clinical symptoms are absent. However, sub-clinical inflammation can still be present. A detailed analysis of the immune status during this inactive state of disease may provide a useful tool to subcategorize patients with subclinical immune activation
Publication Title
Gene expression analysis of peripheral cells for subclassification of pediatric inflammatory bowel disease in remission.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 48 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background In childhood acute lymphoblastic leukemia (ALL), central nervous system (CNS) involvement is rare at diagnosis (1-4%), but more frequent at relapse (~30%). Minimal residual disease diagnostics predict most bone marrow (BM) relapses, but likely cannot predict isolated CNS relapses. Consequently, CNS relapses may become relatively more important. Because of the significant late sequelae of CNS treatment, early identification of patients at risk of CNS relapse is crucial. Methods Gene expression profiles of ALL cells from cerebrospinal fluid (CSF) and ALL cells from BM were compared and differences were confirmed by real-time quantitative PCR. For a selected set of overexpressed genes, protein expression levels of ALL cells in CSF at relapse and of ALL cells in diagnostic BM samples were evaluated by 8-color flow cytometry. Results CSF-derived ALL cells showed a clearly different gene expression profile than BM-derived ALL cells, with differentially-expressed genes (including SCD and OPN) involved in survival and apoptosis pathways and linked to the JAK-STAT pathway. Flowcytometric analysis showed that a subpopulation of ALL cells (>1%) with a CNS signature (SCD positivity and increased OPN expression) was already present in BM at diagnosis in ALL patients who later developed a CNS relapse, but was <1% or absent in virtually all other patients. Conclusions The presence of a subpopulation of ALL cells with a CNS signature at diagnosis may predict isolated CNS relapse. Such information can be used to design new diagnostic and treatment strategies that aim at prevention of CNS relapse with reduced toxicity.
Publication Title
New cellular markers at diagnosis are associated with isolated central nervous system relapse in paediatric B-cell precursor acute lymphoblastic leukaemia.
Sample Metadata Fields
Sex, Age, Time
View Samples- Mus musculus
- 20 Downloadable Samples
- Illumina HiSeq 3000
Description
Purpose: Parturition is delayed by approximately 12 hours in transgenic mice expressing human corticotropin-releasing hormone (CRH) in placenta. The goal of the study was to identify the pathways in reproductive tissues (uterus and placenta) altered by placental expression of human CRH. Methods: Human BAC RP11-366K18 (CHORI) containing human CRH and cis-regulatory region was inserted into the mouse genome by microinjection and random integration to create the BAC1 line. The CRISPR/Cas9 system was used to delete a CRH regulatory element from the BAC1 line to create the CR1 line, eliminating expression of CRH in placenta. Total expression of uterus and placenta by RNA-seq at embryonic day 18.5 were compared between BAC1, CR1, and nontransgenic mice. Results: Genes known to be associated with luteolysis and initiation of parturition (Cav1, Gja1, Oxtr, Ptgs1, Ptgs2) were not differentially expressed in uterus of this model. Conclusions: CRH-mediated delay of parturition is likely independent of luteolysis. Overall design: mRNA-seq was performed on uterus and placenta harvested at embryonic day 18.5 from nontransgenic mice, Tg(BAC1) mice, and Tg(CR1) mice.
Publication Title
Anthropoid primate-specific retroviral element THE1B controls expression of CRH in placenta and alters gestation length.
Sample Metadata Fields
Cell line, Subject
View Samples- Escherichia coli k-12
- 6 Downloadable Samples
- Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
The most important approach to the development of platform organisms for recombinant protein production relies on random mutagenesis and phenotypic selection. Complex phenotypes, including those associated with significant elevated expression and secretion of heterologous proteins, are the result of multiple genomic mutations. Using next generation sequencing, a parent and derivative hypersecreter strain (B41) of Escherichia coli were sequenced with an average coverage of 52.8X and 55X, respectively. A new base-pair calling program, revealed a single nucleotide polymorphism in the B41 genome at position 1,074,787, resulting in translation termination near the N-terminus of a transcriptional regulator protein, RutR, coded by the ycdC gene. We verified the hypersecretion phenotype in a ycdC::Tn5 mutant and observed a 3.4-fold increase in active hemolysin secretion, consistent with the increase observed in B41. mRNA expression profiling showed decreased expression of tRNA-synthetases and some amino acid transporters in the ycdC::Tn5 mutant. This study demonstrates that power of next generation sequencing to characterize mutants leading to successful metabolic engineering strategies for strain improvement.
Publication Title
A single nucleotide polymorphism in ycdC alters tRNA synthetase expression and results in hypersecretion in Escherichia coli.
Sample Metadata Fields
No sample metadata fields
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