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GSE12248
Mus spretus, Mus musculus, Mus musculus x mus spretus
4 Downloadable Samples
Description
Gene expression in self-renewing epithelial tissues is controlled by cis- and trans-activating regulatory factors that mediate responses to exogenous agents capable of causing tissue damage, infection, inflammation, or tumorigenesis. We used network construction methods to analyze the genetic architecture of gene expression in normal mouse skin in a cross between tumor-susceptible Mus musculus and tumor-resistant Mus spretus. We demonstrate that gene expression motifs representing different constituent cell types within the skin such as hair follicle cells, haematopoietic cells, and melanocytes are under separate genetic control. Motifs associated with inflammation, epidermal barrier function and proliferation are differentially regulated in mice susceptible or resistant to tumor development. The intestinal stem cell marker Lgr5 is identified as a candidate master regulator of hair follicle gene expression, and the Vitamin D receptor (Vdr) links epidermal barrier function, inflammation, and tumor susceptibility.
Publication Title
Genetic architecture of mouse skin inflammation and tumour susceptibility.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 55 Downloadable Samples
Description
We developed a mouse model that captures radiation effects on host biology by transplanting unirradiated Trp53 null mammary tissue to sham or irradiated hosts. Gene expression profiles of tumors that arose in irradiated mice are distinct from those that arose in nave hosts.
Publication Title
Murine microenvironment metaprofiles associate with human cancer etiology and intrinsic subtypes.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 53 Downloadable Samples
Description
We used microarrays to detail the role of Polycomb proteins including Ezh2 and Eed in maintaining ES cell identity and executing pluripotency.
Publication Title
EZH1 mediates methylation on histone H3 lysine 27 and complements EZH2 in maintaining stem cell identity and executing pluripotency.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 15 Downloadable Samples
Description
Lung cancer remains the leading cause of cancer death. Genome sequencing of lung tumors from patients with Squamous Cell Carcinoma has identified SMAD4 to be frequently mutated. Here we used a novel mouse model to determine the molecular mechanisms regulated by loss of Smad4 which lead to lung cancer progression. Mice with ablation of Pten and Smad4 in airway epithelium developed metastatic adenosquamous tumors. Comparative transcriptomic and in vivo cistromic analyses determined that loss of PTEN and SMAD4 resulted in activation of the ELF3 and the ErbB2 pathway due to decreased ERRFI1s expression, a negative regulator of ERBB2 in mice and human cells. The combinatorial inhibition of ErbB2 and Akt signaling attenuated tumor progression and cell invasion, respectively. Expression profiles analysis of human lung tumors substantiated the importance of the ErbB2/Akt/ELF3 signaling pathway as both prognostic biomarkers and therapeutic drug targets for treating lung cancer.
Publication Title
ErbB2 Pathway Activation upon Smad4 Loss Promotes Lung Tumor Growth and Metastasis.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 5 Downloadable Samples
Description
Lung cancer is the leading cause of cancer related death in both men and women in the United States. Recently, Smad4 was discovered to be common somatic alteration in human squamous cell lung cancer. Our goal was to delineate the role of Smad4 in lung cancer. We have shown for the first time that the ablation of Pten and Smad4 in the murine airway epithelium harbors a metastatic proximal adeno-squamous lung cancer.
Publication Title
ErbB2 Pathway Activation upon Smad4 Loss Promotes Lung Tumor Growth and Metastasis.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 32 Downloadable Samples
Description
The HSA21-mES Cell Bank includes, in triplicate clones, thirty-two murine orthologs of HSA21 genes, which can be overexpressed in an inducible manner using the Tet-off system integrated in the Rosa26 locus.
Publication Title
A mouse embryonic stem cell bank for inducible overexpression of human chromosome 21 genes.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 27 Downloadable Samples
Description
Origins of the brain tumor, medulloblastoma, from stem cells or restricted pro-genitor cells are unclear. To investigate this, we activated oncogenic Hedgehog signaling in multipotent and lineage-restricted CNS progenitors. We observed that normal unipo-tent cerebellar granule neuron precursors (CGNP) derive from hGFAP+ and Olig2+ rhombic lip progenitors. Hedgehog activation in a spectrum of early and late stage CNS progenitors generated similar medulloblastomas, but not other brain cancers, indicating that acquisition of CGNP identity is essential for tumorigenesis. We show in human and mouse medulloblastoma that cells expressing the glia-associated markers Gfap and Olig2 are neoplastic and that they retain features of embryonic-type granule lineage progenitors. Thus, oncogenic Hedgehog signaling promotes medulloblastoma from lineage-restricted granule cell progenitors.
Publication Title
Acquisition of granule neuron precursor identity is a critical determinant of progenitor cell competence to form Shh-induced medulloblastoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 65 Downloadable Samples
Description
It is widely believed that the carcinogenic action of ionizing radiation is due to targeted DNA damage and resulting mutations, but there is also substantial evidence that non-targeted radiation effects alter epithelial phenotype and the stromal microenvironment. Activation of transforming growth factor 1 (TGF) is a non-targeted radiation effect that mediates cell fate decisions following DNA damage and regulates microenvironment composition; it could either suppress or promote cancer. We asked if such non-targeted radiation effects contribute to carcinogenesis by using a novel radiation chimera model. Unirradiated Trp53 null mammary epithelium was transplanted to the mammary stroma, previously divested of endogenous epithelia, of mice previously exposed to a single low (10 -100 cGy) radiation dose. By 300 days, 100% of transplants in irradiated hosts at either 10 or 100 cGy had developed Trp53 null breast carcinomas compared to 54% in unirradiated hosts. Tumor growth rate was also increased by high, but not low, dose host irradiation. In contrast, irradiation of Tgfb1 heterozygote mice prior to transplantation failed to decrease tumor latency, or increase growth rate at any dose. Host irradiation significantly reduced the latency of invasive ductal carcinoma compared to spindle cell carcinoma. However, irradiation of either host genotype significantly increased the frequency of estrogen receptor negative tumors. These data demonstrate two concepts critical to understanding radiation risks. First, non-targeted radiation effects can significantly promote the frequency and alter the features of epithelial cancer. Second, radiation-induced TGF activity is a key mechanism of tumor promotion.
Publication Title
Radiation acts on the microenvironment to affect breast carcinogenesis by distinct mechanisms that decrease cancer latency and affect tumor type.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
Description
DNA damage plays a major role in neural cell death by necrosis and/or apoptosis. However, our understanding of the molecular mechanisms of neural cell death remains still incomplete. To acquire a global understanding of the various mediators related to DNA damage-induced neural cell death pathways, we performed a whole genomic wide screen in neural stem cells by using a siRNA library. We identified 80 genes required for DNA damage-induced cell death. 14 genes (17.5%) are directly related to cell death and/or apoptosis. 66 genes have not been previously directly linked to DNA damage-induced cell death. Using an integrated approach with functional and bioinformatics analysis, we have uncovered a molecular network containing several partially overlapping and interconnected pathways and/or protein complexes that are required for DNA damage-induced neural cell death. The identification of the network of neural cell death mediators will greatly enhance our understanding of the molecular mechanisms of neural cell death and provide therapeutic targets for nervous system disorders.
Publication Title
High-Content Genome-Wide RNAi Screen Reveals <i>CCR3</i> as a Key Mediator of Neuronal Cell Death.
Sample Metadata Fields
Specimen part, Cell line
View Samples