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Drosophila melanogaster
3 Downloadable Samples
Affymetrix Drosophila Genome Array (drosgenome1)
Description
Mutant embryos lacking maternal and zygotic HOW exhibit defects in mesoderm development. How is an RNA binding protein that regulates the levels of mRNAs by controling RNA metabolism.
Publication Title
Post-transcriptional repression of the Drosophila midkine and pleiotrophin homolog miple by HOW is essential for correct mesoderm spreading.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 2 Downloadable Samples
Illumina Genome Analyzer II
Description
Adult stem cells support tissue homeostasis and repair throughout the life of an individual. However, numerous intrinsic and extrinsic changes occur with age that result in altered stem cell behavior and reduced tissue maintenance and regeneration. In the Drosophila testis, stem cells surround and contact the apical hub, a cluster of somatic cells that express the self-renewal factor Unpaired (Upd), which activates the JAK-STAT pathway in adjacent stem cells. However, aging results in a dramatic decrease in upd expression, with a concomitant loss of germline stem cells (GSCs). Here we present genetic and biochemical data to demonstrate that IGF-II mRNA binding protein (Imp) counteracts endogenous small interfering RNAs to stabilize upd RNA and contribute to maintenance of the niche. However, Imp expression decreases in hub cells of older males, similar to upd, which is due to targeting of Imp by the heterochronic microRNA let-7. Therefore, in the absence of Imp, upd mRNA becomes unprotected and susceptible to degradation. Understanding the mechanistic basis for aging-related changes in stem cell behavior will lead to the development of strategies to treat age-onset diseases and facilitate stem cell based therapies in older individuals. Overall design: Examination of small RNA levels in testes from young (1day old) and aged (30days old) males of Drosophila melanogaster by deep sequencing (using Illumina GAII).
Publication Title
The let-7-Imp axis regulates ageing of the Drosophila testis stem-cell niche.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 125 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Pheochromocytomas, catecholamine-secreting tumors of neural crest origin, are frequently hereditary. However, the molecular basis of the majority of these tumors is unknown. We identified the transmembrane-encoding gene TMEM127 on chromosome 2q11 as a new pheochromocytoma susceptibility gene. In a cohort of 103 samples, we detected truncating germline TMEM127 mutations in approximately 30% of familial tumors and about 3% of sporadic-appearing pheochromocytomas without a known genetic cause. The wild-type allele was consistently deleted in tumor DNA, suggesting a classic mechanism of tumor suppressor gene inactivation. Pheochromocytomas with mutations in TMEM127 are transcriptionally related to tumors bearing NF1 mutations and, similarly, show hyperphosphorylation of mammalian target of rapamycin (mTOR) effector proteins. Accordingly, in vitro gain-of-function and loss-of-function analyses indicate that TMEM127 is a negative regulator of mTOR. TMEM127 dynamically associates with the endomembrane system and colocalizes with perinuclear (activated) mTOR, suggesting a subcompartmental-specific effect. Our studies identify TMEM127 as a tumor suppressor gene and validate the power of hereditary tumors to elucidate cancer pathogenesis.
Publication Title
Germline mutations in TMEM127 confer susceptibility to pheochromocytoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 60 Downloadable Samples
- Illumina HiSeq 2000
Description
Midbrain dopaminergic (mDA) neurons degenerate in Parkinson's disease and are one of the main targets for cell replacement therapies. A comprehensive view of the signals and cell types contributing to mDA neurogenesis is not yet available. By analyzing the transcriptome of the mouse ventral midbrain at tissue and single-cell level during mDA neurogenesis we found that three recently identified radial glia types (Rgl 1-3) contribute to different key aspects of mDA neurogenesis. While Rgl3 expressed most extracellular matrix components and multiple ligands for various pathways controlling mDA neuron development, such as Wnt and Shh, Rgl1-2 expressed most receptors. Moreover, we found that specific transcription factor networks explain the transcriptome expression profiles and suggest a function for each individual radial glia type. Overall design: Triplicate tissue samples from each combination of embryonic day E11.5, E12.5, E13.5, and E14.5 with brain region alar plate, dorsal midbrain, ventral forebrain, ventral hindbrain, and ventral midbrain.
Publication Title
The Matricellular Protein R-Spondin 2 Promotes Midbrain Dopaminergic Neurogenesis and Differentiation.
Sample Metadata Fields
Specimen part, Subject
View Samples
SRP075955- Mus musculus
- 15 Downloadable Samples
- Illumina HiSeq 2000
Description
Investigations into the roles for Pbx1 and its transcriptional network in dopaminergic neuron development and Parkinson's Disease Overall design: Three samples each from dorsal midbrain, forebrain, hindbrain, Alar plate, and ventral midbrain
Publication Title
The Matricellular Protein R-Spondin 2 Promotes Midbrain Dopaminergic Neurogenesis and Differentiation.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To elucidate the mechanism(s) underlying the synergistic interaction between ETV6 and NFKB1, we analyzed the genome-wide transcriptional consequences of single and double knock-downs of the two TFs in U251 cells.
Publication Title
Causal Mechanistic Regulatory Network for Glioblastoma Deciphered Using Systems Genetics Network Analysis.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Atrial fibrillation (AF) is a major risk factor for cardioembolic stroke. Anticoagulant drugs are effective in preventing AF-related stroke. However, the high frequency of anticoagulant-associated major bleeding is a major concern particularly when antiplatelet treatment is simultaneously administered. Here, microarray analysis in peripheral blood cells in eight patients with AF and stroke and eight AF subjects without stroke identified a stroke related gene expression pattern. HSPA1B, which encodes for heat-shock protein 70 kDa (Hsp70), was the most differentially expressed gene. This gene was downregulated in stroke subjects, a finding confirmed further in an independent AF cohort of 200 individuals. Hsp70 knock-out (KO) mice subjected to different thrombotic challenges developed thrombosis significantly earlier than their wild-type (WT) counterparts.
Publication Title
Hsp70 protects from stroke in atrial fibrillation patients by preventing thrombosis without increased bleeding risk.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 7 Downloadable Samples
- IlluminaHiSeq2000
Description
We identified PHF5A as a functional synthetic-lethal hit in glioblastoma stem cells compared to normal neural stem cells. We wanted to perform analysis of RNA isoforms present in glioblastoma or normal neural stem cells with or without PHF5A depletion. We performed shRNA knockdown of PHF5A or used non-silencing shRNA as a control, selected infected cells with puromycin, and isolated RNA for sequencing. Overall design: We analyzed RNA from either normal neural stem cells or two different glioblastoma specimens aster either control knockdown, or two different shRNA sequences against the PHF5A gene transcript.
Publication Title
Genome-wide RNAi screens in human brain tumor isolates reveal a novel viability requirement for PHF5A.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Neuroblastoma (NB) is a neoplasm of the sympathetic nervous system, and is the most common solid tumor of infancy. NBs are very heterogeneous, with a clinical course ranging from spontaneous regression to resistance to all current forms of treatment. High-risk patients need intense chemotherapy, and only 30-40% will be cured. Relapsed or metastatic tumors acquire multi-drug resistance, raising the need for alternative treatments. Owing to the diverse mechanisms that are responsible of NB chemoresistance, we aimed to target epigenetic factors that control multiple pathways to bypass therapy resistance. We found that the SWI/SNF-related, matrix-associated, actin- dependent regulator of chromatin, subfamily a, member 4 (SMARCA4/BRG1) was consistently upregulated in advanced stages of NB, with high BRG1 levels being indicative of poor outcome. Loss-of-function experiments in vitro and in vivo showed that BRG1 is essential for the proliferation of NB cells. Furthermore, whole genome transcriptome analysis revealed that BRG1 controls the expression of key elements of oncogenic pathways such as PI3K/AKT and BCL2, which offers a promising new combination therapy for high-risk NB
Publication Title
BRG1/SMARCA4 is essential for neuroblastoma cell viability through modulation of cell death and survival pathways.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Interactions between the gene products encoded by the mitochondrial and nuclear genomes play critical roles in normal eukaryotic cellular function. Here, we characterized the metabolic and transcriptional properties of A549 lung cancer cells and their isogenic mitochondrial DNA (mtDNA)-depleted rho zero counterparts grown in cell culture and as tumor xenografts in immune-deficient mice. A manuscript summarizing our conclusions is under review.
Publication Title
mtDNA depletion confers specific gene expression profiles in human cells grown in culture and in xenograft.
Sample Metadata Fields
No sample metadata fields
View Samples