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GSE13035
Mus musculus
17 Downloadable Samples
Description
Cellular stress responses can be activated following functional defects in organelles such as mitochondria and the endoplasmic reticulum. Mitochondrial dysfunction caused by loss of the serine protease HtrA2 leads to a progressive movement disorder in mice and has been linked to parkinsonian neurodegeneration in humans. Here we demonstrate that loss of HtrA2 results in transcriptional up-regulation of nuclear genes characteristic of the integrated stress response, including the transcription factor CHOP, selectively in the brain. We also show that loss of HtrA2 results in the accumulation of unfolded proteins in the mitochondria, defective mitochondrial respiration and enhanced production of reactive oxygen species that contribute to the induction of CHOP expression and to neuronal cell death. CHOP expression is also significantly increased in Parkinsons disease patients brain tissue. We therefore propose that this brain-specific transcriptional response to stress may be important in the advance of neurodegenerative diseases.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Fumarate hydratase (FH) mutations cause hereditary leiomyomatosis and renal cell cancer (HLRCC). We have conditionally inactivated the murine ortholog (Fh1) in renal tubular epithelial cells in order to generate an in vivo model of HLRCC. Fh1 knockout mice recapitulates important aspects of HLRCC including the development of renal cysts that overexpress hypoxia inducible factor alpha (Hifa) and Hif-target genes.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 38 Downloadable Samples
Description
The genetic programs that promote retention of self-renewing leukemia stem cells (LSCs) at the apex of cellular hierarchies in acute myeloid leukemia (AML) are not known. In a mouse model of human AML, LSCs exhibit variable frequencies that correlate with the initiating MLL oncogene and are maintained in a self-renewing state by a transcriptional sub-program more akin to that of embryonic stem cells (ESCs) than adult stem cells. The transcription/chromatin regulatory factors Myb, Hmgb3 and Cbx5 are critical components of the program and suffice for Hoxa/Meis-independent immortalization of myeloid progenitors when co-expressed, establishing the cooperative and essential role of an ESC-like LSC maintenance program ancillary to the leukemia initiating MLL/Hox/Meis program. Enriched expression of LSC maintenance and ESC-like program genes in normal myeloid progenitors and poor prognosis human malignancies links the frequency of aberrantly self-renewing progenitor-like cancer stem cells to prognosis in human cancer.
Publication Title
Hierarchical maintenance of MLL myeloid leukemia stem cells employs a transcriptional program shared with embryonic rather than adult stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
Description
The TP53 transcription factor is frequently mutated at later stages of epithelial cancers, indicating a possible role in their invasion and metastasis. Importantly, in most cases rather than a simple loss of function p53 mutation, point mutations of p53 accumulate at the protein level and may have dominant negative functions. This study analyses gene expression differences between mice harbouring p53 mutation who do and do not develop metastasis.
Publication Title
Targeting the LOX/hypoxia axis reverses many of the features that make pancreatic cancer deadly: inhibition of LOX abrogates metastasis and enhances drug efficacy.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
Description
Normal myeloid lineage cell populations (C57BL/6 mice, aged 4-10 weeks, male or female) with three distinct immunophenotypes were prospectively isolated and characterized. In preparation for FACS sorting, bone marrow cells were separated into c-kit+ and c-kit- fractions using an AutoMACS device. C-kit+ cells were further fractionated based on Gr1 and Mac1 expression, and absence of lineage antigen expression (B220, TER119, CD3, CD4, CD8 and IL7R), by cell sorting. C-kit+ Gr1+ Mac1lo/- and c-kit+ Gr1+ Mac1+ displayed cytologic features of undifferentiated hematopoietic cells or myeloblasts, whereas c-kit- Gr1+ Mac1+ cells were mature neutrophils.
Publication Title
Hierarchical maintenance of MLL myeloid leukemia stem cells employs a transcriptional program shared with embryonic rather than adult stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
Description
Leukemia cells from mice with MLL-AF10 AML were fractionated into separate sub-populations on the basis of c-kit expression, which correlates with MLL LSC frequency (Somervaille and Cleary, 2006). The sorted AML sub-populations exhibited substantial differences in their frequencies of AML CFCs/LSCs (mean 14-fold) and morphologic features, consistent with a leukemia cell hierarchy with maturation through to terminally differentiated neutrophils.
Publication Title
Hierarchical maintenance of MLL myeloid leukemia stem cells employs a transcriptional program shared with embryonic rather than adult stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
Description
Epithelial-mesenchymal transition (EMT) has been linked to cancer progression and metastatic propensity. The 4T1 tumor is a clinically relevant model of spontaneous breast cancer metastasis. Here we characterize 4T1-derived cell lines for EMT, in vitro invasiveness and in vivo metastatic ability. Contrary to expectations, the 67NR cells, which form primary tumors but fail to metastasize, express vimentin and N-cadherin, but not E-cadherin. 4T1 cells, however, express E-cadherin, are highly migratory and invasive, and metastasize to multiple sites. The 66cl4 metastatic cells display mixed epithelial and mesenchymal markers, but are less migratory and invasive than 67NR cells. These findings demonstrate that the metastatic ability of breast cancer cells does not correlate with genotypic and phenotypic properties of EMT per se, and suggest that other processes may govern metastatic capability. Gene expression analysis also has not identified differences in EMT markers, but has identified several candidate genes that may influence metastatic ability.
Publication Title
Epithelial-mesenchymal transition (EMT) is not sufficient for spontaneous murine breast cancer metastasis.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 285 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Affymetrix Human Gene 1.1 ST Array profiling of 285 primary medulloblastoma samples.
Publication Title
Subgroup-specific structural variation across 1,000 medulloblastoma genomes.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 4 Downloadable Samples
Description
The analysis of several mammalian genomes has revealed between 20,000 to 30,000 genes in each genome, a number that may seem hard to reconcile with the large number of cell types and complex functions of these organisms. The solution to this paradox partly lies in the large array of transcripts that each gene can potentially generate through usage of alternative promoters and the variable levels of transcripts that each gene produces in different tissues and cell types. Thus, in order to understand the mechanisms that control diverse patterns of gene expression in mammals, it is necessary to accurately define the active promoters and monitor their cell or tissue-dependent activity. Previous high throughput strategies for assaying tissue-specific gene expression have primarily relied on measurements of steady-state transcript levels by microarrays or tag sequencing. Here, we employ a new experimental strategy to identify and characterize tissue specific promoters by integrating genome-wide maps of RNA polymerase II (Pol II) binding, chromatin modifications and gene expression profiles. We applied this strategy to mouse embryonic stem cells (mES), and adult brain, heart, kidney, and liver. Our results delineated 24,363 Pol II binding sites throughout the genome, 91% of which correspond to 5 end annotation based on known transcripts and cap-analysis of gene expression (CAGE) and can be regarded as promoters. A majority of these experimentally defined promoters are active in all tissues, while only 4,396 can be characterized as tissue-specific using a quantitative measure of Pol II occupancy. In general, Pol II occupancy at these tissue specific promoters is correlated with the presence of active histone modification marks. However, a set of mES- specific promoters display persistent levels of H3K4me3 in non-ES tissues despite undetectable Pol II binding and transcript. Broadly, our results expand the knowledge of tissue-specific mammalian genes and provide a resource for understanding the transcriptional programs in mammalian development and differentiation.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
Description
Purpose: We generated extensive transcriptional and proteomic profiles from a Her2-driven mouse model of breast cancer that closely recapitulates human breast cancer. This report makes these data publicly available in raw and processed forms, as a resource to the community. Importantly, we previously made biospecimens from this same mouse model freely available through a sample repository, so researchers can obtain samples to test biological hypotheses without the need of breeding animals and collecting biospecimens.
Publication Title
Proteome and transcriptome profiles of a Her2/Neu-driven mouse model of breast cancer.
Sample Metadata Fields
Sex, Specimen part
View Samples