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SRP077214
Mus musculus
31 Downloadable Samples
Illumina HiSeq 2000
Description
Microcephaly and medulloblastoma result from mutations that compromise genomic stability. We report that Atr, which is mutated in the microcephalic disorder Seckel syndrome, is required to maintain chromosomal integrity during postnatal cerebellar neurogenesis. Atr deletion in cerebellar granule neuron progenitors (CGNPs) induced proliferation-associated DNA damage, p53 activation, apoptosis, and cerebellar hypoplasia. Co-deletions of either Bax and Bak or p53 prevented apoptosis in Atr-deleted CGNPs, but failed to fully rescue cerebellar growth. Atr-deficient CGNPs showed impaired cell cycle checkpoint function and continued to proliferate, accumulating chromosomal abnormalities. RNA-Seq demonstrated that the transcriptional response to Atr-deficient proliferation was p53-driven. Acute Atr inhibition in vivo by nanoparticle-formulated VE-822 reproduced the disruptions seen with Atr deletion. Our data show that p53-driven apoptosis and senescence, and non-apoptotic cell death redundantly limit growth in Atr-deficient progenitors. These overlapping mechanisms that suppress growth in Atr-disrupted CGNPs may be exploited for treatment of CGNP-derived medulloblastoma using Atr inhibition. Overall design: RNA-Seq on total RNA from P3 mouse cerebella of Math1-Cre;Atr-loxP/loxP;Bax-loxP/loxP;Bak--/- (n=5), Math1-Cre;Bax-loxP/loxP;Bak--/- (n=4), Math1-Cre;Atr-loxP/loxP;p53-loxP/loxP (n=5), and Math1-Cre;p53-loxP/loxP (n=3), all run in 2 lanes
Publication Title
ATR maintains chromosomal integrity during postnatal cerebellar neurogenesis and is required for medulloblastoma formation.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
Affymetrix Human Genome U219 Array (hgu219)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
Affymetrix Human Genome U219 Array (hgu219)
Description
Inhibitors of the mechanistic target of rapamycin (mTOR) are currently used to treat advanced metastatic breast cancer. However, whether an aggressive phenotype is sustained through adaptation or resistance to mTOR inhibition remains unknown. Here, complementary studies in human tumors, cancer models and cell lines reveal transcriptional reprogramming that supports metastasis in response to mTOR inhibition. This cancer feature is driven by EVI1 and SOX9. EVI1 functionally cooperates with and positively regulates SOX9, and promotes the transcriptional upregulation of key mTOR pathway components (REHB and RAPTOR) and of lung metastasis mediators (FSCN1 and SPARC). The expression of EVI1 and SOX9 is associated with stem cell-like and metastasis signatures, and their depletion impairs the metastatic potential of breast cancer cells. These results establish the mechanistic link between resistance to mTOR inhibition and cancer metastatic potential, thus enhancing our understanding of mTOR targeting failure.
Publication Title
Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Many neural progenitor cells present in the fetus, but also in adult brain, which play a major role for the reproduction for healingin regeneration of neuronal cells, when differentiated cells are damaged. However, effects of radiation effect on undifferentiated neural progenitor cells remained unclear. The radiation doses of medical exposure, pollution by nuclear power plant accidents, and other exposure of workers; medical workers, airline crews, and astronaut have been focused. In this study, we report the effects of low- to middle- dose doses of radiation on cultured human neural progenitor cells (hNPC) differentiated derived from embryonic stem (ES) cells, which are partially compared with those of human umbilical vein endothelial cell (HUVEC).
Publication Title
Effects of Chronic Low-Dose Radiation on Human Neural Progenitor Cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 34 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Mutant-IDH1-dependent chromatin state reprogramming, reversibility, and persistence.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 2500
Description
Bulk RNA sequencing data from neural progenitor cells under conditions of low or high growth factor and Notch pathway activation Overall design: Cells were treated with high (20 ng/ml EGF and FGF) or low (0.5 ng/ml EGF) recombinant growth factors, with or without Notch pathway inhibitor (DAPT, 10 uM) for 12h.
Publication Title
<i>Cis-</i>activation in the Notch signaling pathway.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 54 Downloadable Samples
- Illumina HiSeq 2500
Description
Renal cell carcinomas with unclassified histology (uRCC) constitute a significant portion of aggressive non-clear cell RCC (nccRCC) that have no standard therapy. The oncogenic drivers in these tumors are unknown. We performed a molecular analysis of 62 high-grade primary uRCC, incorporating targeted cancer gene sequencing, RNA sequencing, Single Nucleotide Polymorphism array, fluorescence in-situ hybridization, immunohistochemistry, and cell-based assays. We identified recurrent somatic mutations in 29 genes, including NF2 (18%), SETD2 (18%), BAP1 (13%), KMT2C (10%), and MTOR (8%). Integrated analysis revealed distinct molecular subsets, including a subset of 26% uRCC characterized by NF2-loss, dysregulated Hippo-YAP pathway and worse survival. Overall design: Analysis of RNA from uRCC with or without NF2-loss
Publication Title
Molecular analysis of aggressive renal cell carcinoma with unclassified histology reveals distinct subsets.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 44 Downloadable Samples
- Illumina HiSeq 2000
Description
The complete transcriptomes of kidney cortex from 3 ?-HIF2aM3 18 month old TG+ male mice and 3 age matched wild type (WT) C57BL/6 male mice were sequenced on an Illumina HiSeq2000 Sequencer. Overall design: Examination of complete transcriptome of kidney cortex between ?-HIF2aM3 TG+ male mice and wild type C57BL/6 male mice
Publication Title
Activation of HIF2α in kidney proximal tubule cells causes abnormal glycogen deposition but not tumorigenesis.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Rattus norvegicus
- 5 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Alterations in the composition of the gut microbiome have an emerging role in brain function and behaviour. We have porposed that short chain fatty acids (SCFA) including propionate and butyrate which are present in the diet and are fermantation products of many gastrointestinal bacteria are contributing environmental factors in autism spectrum disorders (ASD). Here we used the microarray technology to compare global changes in gene expression profiles following exposure of PC12 cells to structurally related SCFA propionate and butyrate each in two different concentrations. Large number of affected genes, common for both SCFA were identified, including genetic networks and GO processes implicated in ASD.
Publication Title
Enteric bacterial metabolites propionic and butyric acid modulate gene expression, including CREB-dependent catecholaminergic neurotransmission, in PC12 cells--possible relevance to autism spectrum disorders.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Analysis of early and late changes in the mouse peritoneal cells in response to E. coli induced sepis. Result provide an insight into the molecular function and pathways expressed at these different time points.
Publication Title
Transcriptomic analysis of peritoneal cells in a mouse model of sepsis: confirmatory and novel results in early and late sepsis.
Sample Metadata Fields
Sex, Treatment
View Samples