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SRP064391
Homo sapiens
24 Downloadable Samples
IlluminaHiSeq2000
Description
There is great medical need for estrogens having favorable pharmacological profiles, supporting desirable activities for menopausal women such as metabolic and vascular protection but lacking stimulatory activities on the breast or uterus. Here, we report the development of structurally novel estrogens with favorable target tissue-selective estrogenic activity. Through a process of structural alteration of the hormone estradiol that preserves essential chemical and physical features of estradiol but greatly moderates its binding affinity for the estrogen receptors (ERs), we obtained Pathway Preferential Estrogens (PaPEs) capable of having interaction with ER that is sufficient to activate the extranuclear-initiated signaling pathway preferentially over the direct nuclear-initiated pathway. PaPE modulate a pattern of gene regulation and cellular and biological processes that result in essentially no stimulation of reproductive and mammary tissues and breast cancer cells, but have a favorable pattern of activity on metabolic tissues and the vasculature. The structural permutation process represents a novel approach to govern the balance in utilization of extranuclear vs. nuclear pathways of ER action to obtain tissue-selective/non-nuclear pathway-preferential estrogens, which should prove to be beneficial for postmenopausal hormone replacement. The approach may also have broad applicability for other members of the nuclear hormone receptor superfamily. Overall design: 24 samples; inhibitor and time course experiments
Publication Title
Design of pathway preferential estrogens that provide beneficial metabolic and vascular effects without stimulating reproductive tissues.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The traditional view of hematopoiesis has been that all the cells of the peripheral blood are the progeny of a unitary homogeneous pool of hematopoietic stem cells (HSCs). Recent evidence suggests that the hematopoietic system is actually maintained by a consortium of HSC subtypes with distinct functional characteristics. We show here that myeloid-biased HSCs (My-HSCs) and lymphoid-biased (Ly-HSCs) can be purified according to their capacity for Hoechst dye efflux in combination with canonical HSC markers.
Publication Title
Distinct hematopoietic stem cell subtypes are differentially regulated by TGF-beta1.
Sample Metadata Fields
Sex, Specimen part
View Samples- Gallus gallus
- 12 Downloadable Samples
- Affymetrix Chicken Genome Array (chicken)
Description
A systematic survey of the transcriptional status of individual segments of the developing chick hindbrain (r1-5) and the adjacent region of the embryonic midbrain (m) during the HH11 stage of chick development
Publication Title
Transcriptomic analysis of midbrain and individual hindbrain rhombomeres in the chick embryo.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 39 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Cerebral palsy is primarily an upper motor neuron disease that results in a spectrum of progressive movement disorders. Secondary to the neurological lesion, muscles from patients with cerebral palsy are often spastic and form debilitating contractures that limit range of motion and joint function. With no genetic component, the pathology of skeletal muscle in cerebral palsy is a response to aberrant neurological input in ways that are not fully understood. This study was designed to gain further understanding of the skeletal muscle response to cerebral palsy using microarrays and correlating the transcriptional data with functional measures. Hamstring biopsies from gracilis and semitendinosus muscles were obtained from a cohort of patients with cerebral palsy (n=10) and typically developing patients (n=10) undergoing surgery. Affymetrix HG-U133A 2.0 chips (n=40) were used and expression data was verified for 6 transcripts using quantitative real-time PCR, as well as for two genes not on the microarray. Chips were clustered based on their expression and those from patients with cerebral palsy clustered separately. Significant genes were determined conservatively based on the overlap of three summarization algorithms (n=1,398). Significantly altered genes were analyzed for over-representation among gene ontologies, transcription factors, pathways, microRNA and muscle specific networks. These results centered on an increase in extracellular matrix expression in cerebral palsy as well as a decrease in metabolism and ubiquitin ligase activity. The increase in extracellular matrix products was correlated with mechanical measures demonstrating the importance in disability. These data lay a framework for further studies and novel therapies.
Publication Title
Transcriptional abnormalities of hamstring muscle contractures in children with cerebral palsy.
Sample Metadata Fields
Sex, Age, Disease, Subject
View Samples- Saccharomyces cerevisiae
- 12 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Analysis of Gal4-directed transcription activation using Tra1 mutants selectively defective for interaction with Gal4.
Sample Metadata Fields
Time
View Samples- Gallus gallus
- 9 Downloadable Samples
- Affymetrix Chicken Genome Array (chicken)
Description
We used microarrays to detail the global program of gene expression underlying gonadotropin-releasing hormone (GnRH) generation and delamination from the olfactory placode.
Publication Title
Serotonin Receptor 1A (HTR1A), a Novel Regulator of GnRH Neuronal Migration in Chick Embryo.
Sample Metadata Fields
Specimen part
View Samples- Saccharomyces cerevisiae
- 6 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
Promoter-specific transcriptional activators (activators) stimulate transcription through direct interactions with one or more components of the transcription machinery, termed the target. Previous studies have provided evidence that the Tra1 subunit of the yeast SAGA (Spt-Ada-Gcn5-acetyltransferase) complex is the target of the yeast activator Gal4. However, several other general transcription factors, in particular the mediator complex, have also been implicated as Gal4 targets. To investigate the essentiality of Tra1 as a target of Gal4, here we derive Tra1 mutants that are selectively defective for interaction with Gal4 in vivo (Gal4 Interaction Defective (GID) mutants). In contrast to wild-type Tra1, Tra1 GID mutants are not recruited by Gal4 to the promoter and cannot support Gal4-directed transcription activation, demonstrating that the Gal4Tra1 interaction is required for Gal4 function. In yeast strains expressing a Tra1 GID mutant, Gal4 promoter binding is unexpectedly also diminished indicating that Gal4 and Tra1 bind cooperatively. Consistent with cooperative binding, we demonstrate that the interaction between Gal4 and Tra1 occurs predominantly on the promoter and not off DNA. Finally, we show that although Tra1 is also targeted by other activators, these interaction are unaffected by GID mutations, revealing an unanticipated specificity of the Gal4-Tra1 interaction.
Publication Title
Analysis of Gal4-directed transcription activation using Tra1 mutants selectively defective for interaction with Gal4.
Sample Metadata Fields
Time
View Samples- Saccharomyces cerevisiae
- 6 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
Promoter-specific transcriptional activators (activators) stimulate transcription through direct interactions with one or more components of the transcription machinery, termed the target. Previous studies have provided evidence that the Tra1 subunit of the yeast SAGA (Spt-Ada-Gcn5-acetyltransferase) complex is the target of the yeast activator Gal4. However, several other general transcription factors, in particular the mediator complex, have also been implicated as Gal4 targets. To investigate the essentiality of Tra1 as a target of Gal4, here we derive Tra1 mutants that are selectively defective for interaction with Gal4 in vivo (Gal4 Interaction Defective (GID) mutants). In contrast to wild-type Tra1, Tra1 GID mutants are not recruited by Gal4 to the promoter and cannot support Gal4-directed transcription activation, demonstrating that the Gal4Tra1 interaction is required for Gal4 function. In yeast strains expressing a Tra1 GID mutant, Gal4 promoter binding is unexpectedly also diminished indicating that Gal4 and Tra1 bind cooperatively. Consistent with cooperative binding, we demonstrate that the interaction between Gal4 and Tra1 occurs predominantly on the promoter and not off DNA. Finally, we show that although Tra1 is also targeted by other activators, these interaction are unaffected by GID mutations, revealing an unanticipated specificity of the Gal4-Tra1 interaction.
Publication Title
Analysis of Gal4-directed transcription activation using Tra1 mutants selectively defective for interaction with Gal4.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 43 Downloadable Samples
- Illumina HiSeq 2000
Description
Since the first generation of induced Pluripotent Stem cells (iPSCs), several reprogramming systems have been used to study its molecular mechanisms. However, the system of choice largely affects the reprogramming efficiency, influencing our view on the mechanisms. Here we demonstrate that reprogramming triggered by less efficient polycistronic reprogramming cassettes not only highlights Mesenchymal-Epithelial Transition (MET) as a roadblock, but also faces more severe difficulties to attain a pluripotent state even post-MET. Also, in contrast to previous findings, more efficient cassettes can reprogram both wild type and Nanog-/- fibroblasts with comparable efficiencies, routes and kinetics, rebutting previous studies that Nanog is critical for iPSC generation. We revealed that the 9 amino acids in the N-terminus of Klf4 in polycistronic reprogramming cassettes are the dominant factor causing these critical differences. Our data establishes that some reprogramming roadblocks are system-dependent, highlighting the need to pursue mechanistic studies with close attention to the systems to better understand reprogramming. Overall design: The aim of the experiment is to compare the reprogramming pathways driven by two different polycistronic cassettes (MKOS and OKMS). We have isolated cells at intermediate stages of both MKOS and OKMS reprogramming and analysed their gene expression profiles. 2N- are CD44- ICAM1-, Nanog-GFP-, 3N- are CD44- ICAM1+, Nanog-GFP-, 3N+ are CD44- ICAM1+, Nanog-GFP+, all from day 10 of reprogramming. MKOS/OKMS iPSCs are established iPSC clones, TNG an Embryonic Stem Cell line carrying a Nanog-GFP reporter published in Chambers et al. Cell, 113, 643-655, from this line TNG MKOS and OKMS Embryonic Stem Cells were generated after targeting the Sp3 locus with the MKOS or the OKMS cassette respectively,E14 a reference Embryonic Stem Cell line and MEF are Mouse Embryonic Fibroblasts either wild type or generaterd from TNG MKOS or OKMS ESCs. D6 is the D6s4B5 iPSC line published in O''Malley et al. Nature, 499, 88-91.
Publication Title
Reprogramming Roadblocks Are System Dependent.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Allergic asthma is a complex trait. Several approaches have been used to identify biomarkers involved in this disease. This study aimed at demonstrating the relevance and validity of microarrays in the definition of allergic asthma expression pattern. The authors compared the transcript expressions of bronchial biopsy of 2 different microarray experiments done 2 years apart, both including nonallergic healthy and allergic asthmatic subjects (n = 4 in each experiment). U95Av2 and U133A GeneChips detected respectively 89 and 40 differentially expressed genes. Fifty-five percent of the U133A genes were previously identified with the U95Av2 arrays. The immune signaling molecules and the proteolytic enzymes were the most preserved categories between the 2 experiments, because 3/4 of the genes identified by the U133A were also significant in the U95Av2 study for both categories. These results demonstrate the relevance of microarray experiments using bronchial tissues in allergic asthma. The comparison of these GeneChip studies suggests that earlier microarray results are as relevant as actual ones to target new genes of interest, particularly in function categories linked to the studied disease. Moreover, it demonstrates that microarrays are a valuable technology to target novel allergic asthma pathways as well as biomarkers.
Publication Title
A comparison of two sets of microarray experiments to define allergic asthma expression pattern.
Sample Metadata Fields
Specimen part, Disease
View Samples