The concept of tumor stem cells (TSCs) provides a new paradigm for understanding tumor biology, although it remains unclear whether TSCs will prove to be a more robust model than traditional cancer cell lines. We demonstrate marked phenotypic and genotypic differences between primary human tumor-derived TSCs and their matched glioma cell lines. TSCs derived directly from primary glioblastomas harbor extensive similarities to normal NSC and recapitulate the genotype, gene expression patterns and in vivo biology of human glioblastomas. By contrast, the matched, traditionally grown tumor cell lines do not secondary to in vitro genomic alterations. These findings suggest that TSCs may be a more reliable model than many commonly utilized cancer cell lines for understanding the biology of primary human tumors. Analysis of gene expression data is described in Lee et al., Cancer Cell, 2006.
Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serum-cultured cell lines.
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View SamplesTranscriptome analysis of growth hormone dependant genes in glomerular podocytes
Growth hormone (GH)-dependent expression of a natural antisense transcript induces zinc finger E-box-binding homeobox 2 (ZEB2) in the glomerular podocyte: a novel action of gh with implications for the pathogenesis of diabetic nephropathy.
Specimen part, Treatment
View SamplesGliomas are mostly incurable secondary to their diffuse infiltrative nature. Thus, specific therapeutic targeting of invasive glioma cells is an attractive concept. As cells exit the tumor mass and infiltrate brain parenchyma, they closely interact with a changing micro-environmental landscape that sustains tumor cell invasion.
Identification of molecular pathways facilitating glioma cell invasion in situ.
Specimen part
View SamplesAn important question for the use of the mouse as a model for studying human disease is the degree of functional conservation of genetic control pathways from human to mouse. The human placenta and mouse placenta show structural similarities but there has been no systematic attempt to assess their molecular similarities or differences. We built a comprehensive database of protein and microarray data for the highly vascular exchange region micro-dissected from the human and mouse placenta near-term. Abnormalities in this region are associated with two of the most common and serious complications of human pregnancy, maternal preeclampsia (PE) and fetal intrauterine growth restriction (IUGR), each disorder affecting ~5% of all pregnancies.
Comparative systems biology of human and mouse as a tool to guide the modeling of human placental pathology.
No sample metadata fields
View SamplesThis is Rembrandt gene expression data (Affymetrix HG-U133Plus2).
Rembrandt: helping personalized medicine become a reality through integrative translational research.
Specimen part, Disease, Disease stage
View SamplesAnalyses of six Ts1Cje (Down syndrome) and six normal littermate (2N) mouse brains at postnatal day 0.
Dosage-dependent over-expression of genes in the trisomic region of Ts1Cje mouse model for Down syndrome.
No sample metadata fields
View SamplesAnalyses of six Ts1Cje (Down syndrome) and six normal littermate (2N) mouse brains at postnatal day 0.
Dosage-dependent over-expression of genes in the trisomic region of Ts1Cje mouse model for Down syndrome.
No sample metadata fields
View SamplesAnalyses of six Ts1Cje (Down syndrome) and six normal littermate (2N) mouse brains at postnatal day 0.
Dosage-dependent over-expression of genes in the trisomic region of Ts1Cje mouse model for Down syndrome.
No sample metadata fields
View SamplesMutations of STAT3 underlie the autosomal dominant form of hyper-immunoglobulin E syndrome (HIES). STAT3 has critical roles in immune cells and thus, hematopoietic stem cell transplantation (HSCT), might be a reasonable therapeutic strategy in this disease. However, STAT3 also has critical functions in non-hematopoietic cells and dissecting the protean roles of STAT3 is limited by the lethality associated with germline deletion of Stat3. Thus, predicting the efficacy of HSCT for HIES is difficult. To begin to dissect the importance of STAT3 in hematopoietic and non-hematopoietic cells as it relates to HIES, we generated a mouse model of this disease. We found that these transgenic mice recapitulate multiple aspects of HIES, including elevated serum IgE and failure to generate Th17 cells. We found that these mice were susceptible to bacterial infection that was partially corrected by HSCT using wild type bone marrow, emphasizing the role played by the epithelium in the pathophysiology of HIES.
A mouse model of HIES reveals pro- and anti-inflammatory functions of STAT3.
Specimen part
View SamplesWe developed a computational framework that integrates chromosomal copy number and gene expression data for detecting aberrations that promote cancer progression. We demonstrate the utility of this framework using a melanoma dataset. Our analysis correctly identified known drivers of melanoma and predicted multiple novel tumor dependencies. Two dependencies, TBC1D16 and RAB27A, confirmed empirically, suggest that abnormal regulation of protein trafficking contributes to proliferation in melanoma. Together, these results demonstrate the ability of integrative Bayesian approaches to identify novel candidate drivers with biological, and possibly therapeutic, importance in cancer.
An integrated approach to uncover drivers of cancer.
Cell line
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