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SRP131324
Homo sapiens
6 Downloadable Samples
Illumina HiSeq 2000
Description
Hepatocellular carcinoma (HCC) accounts for the majority of malignant liver tumors and results in many deaths each year, emphasizing the need for new therapies. The protein-protein interaction between menin and histone methyltransferase Mixed Lineage Leukemia 1 (MLL1) plays an important role in the development of HCC, implying that pharmacologic inhibition of this interaction could lead to new therapeutic strategy for the HCC patients. Therefore, we performed RNA sequencing experiment to determine the transcriptome change in the HepG2 cells upon treatment of MI-503, a small molecule inhibitor of the menin-MLL1 interaction with optimized drug-like properties Overall design: HepG2 cells were plated in the 12-well plates at the initial concentration of 0.4x106 cells/ml and treated with 3 µM MI-503 or DMSO (0.25%) in triplicates. After 3 days of treatment viable cell number was adjusted to the original concentration in the DMSO treated samples and the same dilution factor was used to adjust cell number in the MI-503 treated cells. Media was changed and compound or DMSO was re-supplied at that time. Cells were harvested after 3 more days of incubation.
Publication Title
Pharmacologic Inhibition of the Menin-MLL Interaction Leads to Transcriptional Repression of <i>PEG10</i> and Blocks Hepatocellular Carcinoma.
Sample Metadata Fields
Treatment, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
Affymetrix Human Genome U219 Array (hgu219)
Description
Chromosomal translocations affecting Mixed Lineage Leukemia (MLL) gene result in acute leukemias resistant to therapy. The leukemogenic activity of MLL fusion proteins is dependent on their interaction with menin, providing basis for therapeutic intervention. Here we report development of novel, highly potent and orally bioavailable small molecule inhibitors of the menin-MLL interaction, MI-463 and MI-503, show their profound effects in MLL leukemia cells and substantial survival benefit in mice models of MLL leukemia. Finally, we demonstrate efficacy of these compounds in primary samples derived from MLL leukemia patients. Overall, we demonstrate for the first time that pharmacologic inhibition of the menin-MLL interaction represents an effective treatment for MLL leukemias in vivo and provide advanced molecular scaffold for clinical lead identification.
Publication Title
Pharmacologic inhibition of the Menin-MLL interaction blocks progression of MLL leukemia in vivo.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 11 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Acetylation of transcriptional regulators is normally dynamically regulated by nutrient status but is often persistently elevated in nutrient-excessive obesity conditions. We investigated the functional consequences of such aberrantly elevated acetylation of the nuclear receptor FXR as a model. Proteomic studies identified K217 as the FXR acetylation site in diet-induced obese mice. In vivo studies utilizing acetylation-mimic and -defective K217 mutants and gene expression profiling revealed that FXR acetylation increased proinflammatory gene expression, macrophage infiltration, and liver cytokine and triglyceride levels, impaired insulin signaling, and increased glucose intolerance. Mechanistically, acetylation of FXR blocked its interaction with the SUMO ligase PIASy and inhibited SUMO2 modification at K277, resulting in activation of inflammatory genes. SUMOylation of agonist-activated FXR increased its interaction with NF-B but blocked that with RXR, so that SUMO2-modified FXR was selectively recruited to and trans-repressed inflammatory genes without affecting FXR/RXR target genes. A dysregulated Acetyl/SUMO switch of FXR in obesity may serve as a general mechanism for diminished anti-inflammatory response of other transcriptional regulators and provide potential therapeutic and diagnostic targets for obesity-related metabolic disorders.
Publication Title
A dysregulated acetyl/SUMO switch of FXR promotes hepatic inflammation in obesity.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Arabidopsis thaliana
- 4 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Phloem-feeding pests cause extensive crop damage throughout the world yet little is understood about how plants perceive and defend themselves from these threats. The silverleaf whitefly (SLWF; Bemisia tabaci type B) is a good model for studying phloem-feeding insect-plant interactions as SLWF nymphs cause little wounding and have a long, continuous interaction with the plant. Using the Arabidopsis ATH1 GeneChip, the global responses to Silverleaf Whitefly 2nd instar feeding were examined.
Publication Title
Arabidopsis transcriptome changes in response to phloem-feeding silverleaf whitefly nymphs. Similarities and distinctions in responses to aphids.
Sample Metadata Fields
Age
View Samples- Homo sapiens
- 16 Downloadable Samples
- IlluminaHiSeq2000
Description
Staphylococcus aureus can cause serious skin, respiratory, and other life-threatening invasive infections in humans, and methicillin-resistant S. aureus (MRSA) strains have been acquiring increasing antibiotic resistance. While MRSA was once mainly considered a hospital-acquired infection, the emergence of new strains, some of which are pandemic, has resulted in community-acquired MRSA infections that often present as serious skin infections in otherwise healthy individuals. Accordingly, defining the mechanisms that govern the activation and regulation of the immune response to MRSA is clinically important and could lead to the discovery of much needed rational targets for therapeutic intervention. Because the cytokine thymic stromal lymphopoetin (TSLP) is highly expressed by keratinocytes of the skin3, we investigated its role in host-defense against MRSA. Here we demonstrate that TSLP acts on neutrophils to increase their killing of MRSA. In particular, we show that both mouse and human neutrophils express functional TSLP receptors. Strikingly, TSLP enhances mouse neutrophil killing of MRSA in both an in vitro whole blood killing assay and an in vivo skin infection model. Similarly, TSLP acts directly on purified human blood neutrophils to reduce MRSA burden. Unexpectedly, we demonstrate that TSLP mediates these effects both in vivo and in vitro by engaging the complement C5 system. Thus, TSLP increases MRSA killing in a neutrophil- and complement-dependent manner, revealing a key connection between TSLP and the innate complement system, with potentially important therapeutic implications for control of MRSA infection. Overall design: mRNA expression analysis. 16 samples are from 2 donors, 8 samples per donor, 2 time points (4hr and 16 hr), and 4 conditions (control, TSLP treated, Heat Killed MRSA treated, and TSLP+HKM treated) .
Publication Title
A TSLP-complement axis mediates neutrophil killing of methicillin-resistant <i>Staphylococcus aureus</i>.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
In the ovarian follicle, maturation of the oocyte increases in the presence of somatic cells called cumulus cells (CCs). These cells form a direct barrier between the oocyte and external environment. Thanks to bidirectional communication, they have a direct impact on the oocyte, its quality and development potential. Understanding the genetic profile of CCs appears to be important in elucidating the physiology of oocytes. In this work, CCs were subjected to in vitro long-term culture. RNA was collected after 1, 7, 15 and 30 days of culture. Expression microarrays were used for analysis, which allowed to identify groups of genes characteristic for particular cellular processes.
Publication Title
Human Cumulus Cells in Long-Term In Vitro Culture Reflect Differential Expression Profile of Genes Responsible for Planned Cell Death and Aging-A Study of New Molecular Markers.
Sample Metadata Fields
Sex, Specimen part
View Samples- Sus scrofa
- 6 Downloadable Samples
- Porcine Gene 1.1 ST Array (porgene11st)
Description
The proper mammalian oocytes maturation is recognized as reaching MII stage and accumulation of mRNA and proteins in cell cytoplasm following fertilization. The proper course of folliculogenesis and oogenesis is orchestrated with morphogenesis significantly influencing further zygote formation and embryos growth. This study was aimed to determinate new transcriptomic markers of porcine oocytes morphogenesis associated with cell maturation capacity.
Publication Title
"Cell Migration" Is the Ontology Group Differentially Expressed in Porcine Oocytes Before and After In Vitro Maturation: A Microarray Approach.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 40 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
To identify genes important in fetal preparation for birth.
Publication Title
Developmental control of the Nlrp6 inflammasome and a substrate, IL-18, in mammalian intestine.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 151 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Three different cell populations (6 healthy B-lymphocytes, 6 leukemic CLL B-lymphocyte of indolent form and 5 leukemic CLL B-lymphocyte of aggressive form) were stimulated in vitro with an anti-IgM antibody, activating the B-cell receptor (BCR). We analyzed the gene expression at 4 time points (60, 90, 210 and 390 minutes). Each gene expression measurement is performed both in stimulated cells and in control unstimulated cells.
Publication Title
Reverse-engineering the genetic circuitry of a cancer cell with predicted intervention in chronic lymphocytic leukemia.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 26 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To examine the possibility that biochemical or molecular signatures of endometrium may prove to be more useful, we have investigated whole genome molecular phenotyping (54,600 genes/ESTs) of this tissue sampled across the cycle in 28 normo-ovulatory women, using high-density oligonucleotide microarrays. The results demonstrate that endometrial samples obtained by two different sampling techniques (biopsy and curetting hysterectomy specimens) from subjects who are as normal as possible in a human study and 4 including those with unknown histology, can be classified by their molecular signatures and correspond to known phases of the menstrual cycle with identical results using two independent analytical methods. Also, the results enable global identification of biological processes and molecular mechanisms that occur dynamically in the endometrium in the changing steroid hormone milieu across the menstrual cycle in normo-ovulatory women. The results underscore the potential of gene expression profiling for developing molecular diagnostics of endometrial normalcy and abnormalities and identifying molecular targets for therapeutic purposes in endometrial disorders.
Publication Title
Molecular phenotyping of human endometrium distinguishes menstrual cycle phases and underlying biological processes in normo-ovulatory women.
Sample Metadata Fields
Age
View Samples