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GSE70271
Mus musculus
58 Downloadable Samples
Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Tumors from 5-6 month old KrasLA mice were dissected. Gene expression analysis on U74A affy chips. 19 normal lungs from age matched controls were also includeed
Publication Title
Comparison of gene expression and DNA copy number changes in a murine model of lung cancer.
Sample Metadata Fields
Sex, Age, Disease, Disease stage
View Samples- Mus musculus
- 4 Downloadable Samples
NextSeq 500
Description
Introduction: Glioma stem cells isolated from human glioblastomas are resistant to radiation and cytotoxic chemotherapy and may drive tumor recurrence. Treatment efficacy may depend on the presence of glioma stem cells, expression of DNA repair enzymes such as methylguanine methyltransferase (MGMT), or transcriptome subtype. Methods: To model genetic alterations in the core signaling pathways of human glioblastoma, we induced conditional Rb knockout, Kras activation, and Pten deletion mutations in cortical murine astrocytes. Serial neurosphere culture, multi-lineage differentiation, and orthotopic transplantation were used to assess whether these mutations induced de-differentiation of cortical astrocytes into glioma stem cells. Efficacy of radiation and temozolomide was examined in vitro and in an allograft model in vivo. The effects of radiation on transcriptome subtype was examined by expression profiling. Results: G1/S-defective, Rb knockout astrocytes gained unlimited self-renewal and multi-lineage differentiation capacity, in both the presence and absence of Kras and Pten mutations. Only triple mutant astrocytes formed serially-transplantable glioblastoma allografts. Triple mutant astrocytes and allografts were sensitive to radiation, but expressed Mgmt and were resistant to temozolomide. Radiation induced a shift in transcriptome subtype of glioblastoma allografts from proneural to mesenchymal. Conclusion: A defined set of core signaling pathway mutations induces de-differentiation of cortical murine astrocytes into glioma stem cells. This non-germline genetically engineered mouse model mimics human proneural glioblastoma on histopathological, molecular, and treatment response levels. It may be useful in dissecting the genetic and cellular mechanisms of treatment resistance and developing more effective therapies. Overall design: Investigation of chromatin accessibility in astrocytes and glioblastoma cell lines
Publication Title
Core pathway mutations induce de-differentiation of murine astrocytes into glioblastoma stem cells that are sensitive to radiation but resistant to temozolomide.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
To investigate transcriptional differences between HCM and WT cells Overall design: Examination of HCM vs WT Cells, with 3 replicates of each sample
Publication Title
A Contraction Stress Model of Hypertrophic Cardiomyopathy due to Sarcomere Mutations.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Arabidopsis thaliana
- 19 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Effects of aneuploidy on gene expression in Arabidopsis thaliana containing extra copies of chromosome 5.
Publication Title
Effects of aneuploidy on genome structure, expression, and interphase organization in Arabidopsis thaliana.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The Wnt signaling pathway is deregulated in over 90% of human colorectal cancers. Catenin, the central signal transducer of the Wnt pathway, can directly modulate gene expression by interacting with transcription factors of the TCF/LEF-family. In the present study we investigate the role of Wnt signaling in the homeostasis of intestinal epithelium using tissue-specific, inducible beta-catenin gene ablation in adult mice. Block of Wnt/beta-catenin signaling resulted in rapid loss of transient-amplifying cells and crypt structures. Importantly, intestinal stem cells were induced to terminally differentiate upon deletion of beta-catenin resulting in a complete block of intestinal homeostasis and fatal loss of intestinal function. Transcriptional profiling of mutant crypt mRNA isolated by laser capture micro dissection confirmed those observations and allowed to identify genes potentially responsible for the functional preservation of intestinal stem cells.
Publication Title
Wnt/beta-catenin is essential for intestinal homeostasis and maintenance of intestinal stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 48 Downloadable Samples
- Affymetrix Drosophila Genome Array (drosgenome1)
Description
Identification of Hox gene downstream genes at embryonic stages 11 and 12<br></br><br></br>Functional diversification of body parts is dependent on the formation of specialized structures along the various body axes. In animals, region-specific morphogenesis along the anterior-posterior axis is controlled by a group of conserved transcription factors encoded by the Hox genes. Although it has long been assumed that Hox proteins carry out their function by regulating distinct sets of downstream genes, only a small number of such genes have been found, with very few having direct roles in controlling cellular behavior. We have quantitatively identified hundreds of Hox downstream genes in Drosophila by microarray analysis, and validated many of them by in situ hybridizations on loss- and gain-of-function mutants. One important finding is that Hox proteins, despite their similar DNA binding properties in vitro, have highly specific effects on the transcriptome in vivo, as expression of many downstream genes responds primarily to a single Hox protein. In addition, a large fraction of downstream genes encodes realizator functions, which directly affect morphogenetic processes, such as orientation and rate of cell divisions, cell-cell adhesion and communication, cell shape and migration, or cell death. Focusing on these realizators, we provide a framework for the morphogenesis of the maxillary segment. Since the genomic organization of Hox genes and the interaction of Hox proteins with specific cofactors are conserved in vertebrates and invertebrates, and similar classes of downstream genes are regulated by Hox proteins across the metazoan phylogeny, our findings represent a first step towards a mechanistic understanding of morphological diversification within a species as well as between species.
Publication Title
Comparative analysis of Hox downstream genes in Drosophila.
Sample Metadata Fields
Age, Time
View Samples- Caenorhabditis elegans
- 47 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Transgenic animals were engineered to express human amyloid peptide controlled by a muscle-specific, heat-inducible promoter. At low temperatures (16C) Abeta expression is minimal, while at higher temperatures (20-25C) Abeta accummulates in large quantities and causes paralysis.
Publication Title
Identifying Aβ-specific pathogenic mechanisms using a nematode model of Alzheimer's disease.
Sample Metadata Fields
Time
View Samples- Arabidopsis thaliana
- 44 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Plants exhibit a robust transcriptional response to gamma radiation which includes the induction of transcripts required for homologous recombination and the suppression of transcripts that promote cell cycle progression. Various DNA damaging agents induce different spectra of DNA damage as well as collateral damage to other cellular components and therefore are not expected to provoke identical responses by the cell.
Publication Title
High atomic weight, high-energy radiation (HZE) induces transcriptional responses shared with conventional stresses in addition to a core "DSB" response specific to clastogenic treatments.
Sample Metadata Fields
Age, Time
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Here we identify HOXA5 as an important repressor of intestinal stem cell fate in vivo and identify a reciprocal feedback between HOXA5 and Wnt signaling. HOXA5 is suppressed by the Wnt pathway to maintain stemness and becomes active only outside the intestinal crypt where it inhibits Wnt signaling to enforce differentiation. In colon cancer, HOXA5 is down-regulated and its re-expression induces loss of the cancer stem cell phenotype preventing tumor progression and metastasis. Tumor regression by HOXA5 induction can be triggered by retinoids, which represents a tangible means to treat colon cancer by eliminating cancer stem cells.
Publication Title
HOXA5 Counteracts Stem Cell Traits by Inhibiting Wnt Signaling in Colorectal Cancer.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 108 Downloadable Samples
- Illumina HiSeq 2500
Description
Female C57BL/6J mice hemizygous for the 5XFAD transgene (MMRRC Stock No #34848-JAX) were bred to males from BXD strains, which do not carry the 5XFAD transgene. The resulting F1 progeny were monitored throughout their lifespan to evaluate the effect of genetic background on cognitive and pathological traits. All of the mice were fear conditioned and sacrificed within 30 minutes of testing. On the sample records, the characteristics: age field provides the age at which fear conditioning, sacrifice, and tissue collection occurred. Samples here come from various AD-BXD lines and their non-transgenic (Ntg) littermate counterparts at either 6 or 14 months of age. Overall design: 133 samples, 64 Ntg and 69 AD. For final by-strain analysis, samples were averaged into strain/age/genotype/sex groups (For example, all D2 6mo 5XFAD males were averaged for final by-strain analysis)
Publication Title
Harnessing Genetic Complexity to Enhance Translatability of Alzheimer's Disease Mouse Models: A Path toward Precision Medicine.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples