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GSE68326
Mus musculus
5 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Ebf genes regulate differentiation of several cell type. Ebf2 is expressed in Schwann cells and Ebf2-/- mice show among other phenotypical abnormalities a delay in the onset of myelination associated to a decreased expression of genes regulating myelination. In addition at one month of age Ebf2-/- mice show decreased motor conduction velocity and morphological alteration in sciatic nerves. Ebf2 target genes are unknown. To identify Ebf2 target genes with a role in myelination, we compared the expression profiles of sciatic nerves isolated from P2 Wt and Ebf2-/- mice by microarray analysis.
Publication Title
The Transcription Factors EBF1 and EBF2 Are Positive Regulators of Myelination in Schwann Cells.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 16 Downloadable Samples
Illumina HiSeq 2500
Description
Thousands of long non-coding RNAs (lncRNAs) have been identified in the human genome, but specific biological functions and biochemical mechanisms have been discovered for only about a dozen lncRNAs. One specific lncRNA, Non-coding RNA Activated by DNA Damage (NORAD), has recently been shown by genetic deletion to be required for maintaining genomic stability, but its molecular mechanism is unknown. Here, we combine RNA antisense purification (RAP) and quantitative mass spectrometry to identify proteins that directly interact with NORAD in living cells. We show that NORAD interacts with proteins involved in DNA replication and repair in steady-state cells and localizes to the nucleus upon stimulation with replication stress or DNA damage. In particular, NORAD interacts with RBMX (an emerging component of the DNA-damage response) and encodes the strongest RBMX-binding site in the transcriptome. We demonstrate that NORAD controls the ability of RBMX to assemble a ribonucleoprotein complex, which we term NORAD-Activated Ribonucleoprotein Complex 1 (NARC1), containing known suppressors of genomic instability: topoisomerase I (TOP1), ALYREF and the PRPF19/CDC5L complex. Cells depleted of NORAD or RBMX display an increased frequency of chromosome segregation errors, reduced replication-fork velocity and altered cell cycle progression phenotypes that are mechanistically linked to TOP1 and PRPF19/CDC5L function. Expression of NORAD in trans can rescue defects caused by NORAD depletion, but rescue is significantly impaired when the RBMX-binding site in NORAD is deleted. Our results demonstrate that the interaction between NORAD and RBMX is important for NORAD function and that NORAD is required for the assembly of a previously unknown topoisomerase complex (NARC1) that contributes to maintaining genomic stability. Moreover, we uncover a novel function for lncRNAs in modulating the ability of an RNA-binding protein to assemble a higher-order ribonucleoprotein complex. Overall design: We examined gene expression changes and alternative splicing events in wildtype and NORAD depleted cells using RNA sequencing.
Publication Title
The NORAD lncRNA assembles a topoisomerase complex critical for genome stability.
Sample Metadata Fields
Cell line, Subject, Time
View Samples- Mus musculus
- 42 Downloadable Samples
- Illumina HiSeq 2500
Description
Using integrated genomics we identify a role for CLEC12A in antibacterial autophagy. Clec12a-/- mice are more susceptible to bacterial infection and CLEC12A deficient cells exhibit impaired antibacterial autophagy. We used transcriptional profilinf to understand the role of CLEC12A in the response to Salmonella and Listeria. Overall design: Bone marrow-derived macrophages from WT or Clec12a-/- mice were infected with Salmonella enterica serovar Typhimurium or Listeria monocytogenes. Cells were harvested at 0,3,6, and 24hours post-infection for RNA analysis. Please note that single-end sequencing was performed but two files: R1 files that contained the sample barcodes (19 or 17bp reads) and R2 files that contained the single-end-sequenced 46bp cDNA reads were generated. Since the barcode info is mostly redundant, only R2 reads were submitted (described in ''raw_file_readme.txt'').
Publication Title
Integrated Genomics of Crohn's Disease Risk Variant Identifies a Role for CLEC12A in Antibacterial Autophagy.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 24 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Cytokine-induced beta-cell apoptosis is a key event for the death of pancreatic beta cells in the development of type-1 diabetes. We identified BRD0476 as a novel suppressor of cytokine-induced beta-cell apoptosis.
Publication Title
Kinase-Independent Small-Molecule Inhibition of JAK-STAT Signaling.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Dysregulated oncogenic serine/threonine kinases play a pathological role in diverse forms of malignancies, including multiple myeloma (MM), and thus represent potential therapeutic targets. Here, we evaluated the biological and functional role of p21-activated kinase 4 (PAK4), and its potential as a new target in MM for clinical applications. PAK4 promoted MM cell growth and survival via activation of MM survival signaling pathways, including the MEK-ERK pathway. Furthermore, treatment with orally bioavailable PAK4 allosteric modulator (KPT-9274) significantly impacted MM cell growth and survival in a large panel of MM cell lines and primary MM cells alone and in the presence of bone marrow microenvironment. Intriguingly, we have identified FGFR3 as a novel binding partner of PAK4 and observed significant activity of KPT-9274 against t(4;14)-positive MM cells. These data support PAK4 as an oncogene in myeloma, and provide the rationale for the clinical evaluation of PAK4 modulator in myeloma.
Publication Title
Functional role and therapeutic targeting of p21-activated kinase 4 in multiple myeloma.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Drosophila melanogaster
- 8 Downloadable Samples
- Illumina Genome Analyzer IIx, Illumina HiSeq 2000
Description
mRNA sequencing was used to identify genome wide transcriptional changes occuring in fly heads in response to spermidine feeding. This study shed light on the molecular mechanisms through wich spermidine can protect against age-dependent memory impairment. Overall design: mRNA profiles from 3 and 10 day old Drosophila melanogaster heads were generated in duplicate by deep sequencing using Illumina GAIIx. mRNA profiles from flies that were fed food with 5mM spermidine were compared to profiles from flies that had no spermidine in thier food.
Publication Title
Restoring polyamines protects from age-induced memory impairment in an autophagy-dependent manner.
Sample Metadata Fields
Age, Specimen part, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We identified two isoforms of human MKL1 that differ in their N-terminal domains. Since MKL1 is a transcriptional coactivator of SRF and regulates many SRF target genes, we wanted to analyze if transcription is differentially regulated by the two isoforms upon stimulation of the Rho-actin-MKL1-SRF pathway.
Publication Title
TGF-β-induced differentiation into myofibroblasts involves specific regulation of two MKL1 isoforms.
Sample Metadata Fields
Cell line
View Samples- Rattus norvegicus
- 18 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Cyclosporin A induces expression of proapoptotic factors when cells are challenged by increased tonicity
Publication Title
Cyclosporin-A induced toxicity in rat renal collecting duct cells: interference with enhanced hypertonicity induced apoptosis.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Our understanding of how mesodermal tissue is formed, has been limited by the absence of specific and reliable markers of early mesoderm commitment. We report that mesoderm commitment from human embryonic stem cells (hESC) is initiated by Epithelial to Mesenchymal transition (EMT) as shown by gene expression profiling and by reciprocal changes in expression of the cell surface proteins, EpCAM/CD326 and NCAM/CD56. Molecular and functional assays reveal that CD326negCD56+ cells, generated from hESC in the presence of activin A, BMP4, VEGF and FGF2, represent a novel, multi-potent mesoderm-committed progenitor population. CD326negCD56+ progenitors are unique in their ability to generate all mesodermal lineages including hematopoietic, endothelial, mesenchymal (bone, cartilage, fat, fibroblast), smooth muscle and cardiomyocytes, while lacking the pluripotency of hESC. CD326negCD56+ cells are the precursors of previously reported, more lineage-restricted mesodermal progenitors. These findings present a novel approach to study how germ layer specification is regulated, and offer a unique target for tissue engineering.
Publication Title
Mapping the first stages of mesoderm commitment during differentiation of human embryonic stem cells.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 19 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Desmin is a cytoskeletal protein in muscle involved in integrating cellular space and transmitting forces. In this study we sought to determine the combinatory effects of desmin deletion, aging and eccentric exercise on skeletal muscle at the transcriptional level across many pathways of muscle physiology.
Publication Title
Role of the cytoskeleton in muscle transcriptional responses to altered use.
Sample Metadata Fields
Specimen part, Treatment
View Samples