Mice that develop benign cartilage lesions due to overexpression of Gli2 in chondrocytes developed lesions similar to chondrosarcomas when also deficient in p53. Gli2 overexpression and p53 deficiency had opposing effects on chondrocyte differentiation, but had additive effects negatively regulating apoptosis. Regulation of Igfbp3 expression and IGF signaling by Gli and p53 integrated their effect on apoptosis. Treatment of human chondrosarcomas or fetal mouse limbs explants with IGFBP3 or by blocking IGF increased the apoptosis rate, and mice expressing Gli2 developed substantially fewer tumors when also deficient for Igf2. IGF signaling meditated apoptosis regulates the progression to malignant chondrosarcoma.
Gli2 and p53 cooperate to regulate IGFBP-3- mediated chondrocyte apoptosis in the progression from benign to malignant cartilage tumors.
Cell line
View SamplesStandardization of MSC manufacturing is urgently needed to facilitate comparison of clinical trial results. Here, we compare gene expression of MSC generated by the adaptation of a proprietary method for isolation and cultivation of a specific umbilical cord tissue-derived population of Mesenchymal Stromal Cells (MSCs)
Towards an advanced therapy medicinal product based on mesenchymal stromal cells isolated from the umbilical cord tissue: quality and safety data.
No sample metadata fields
View SamplesOsteoarthritis (OA) is a common degenerative disease of the joint. Data from our lab indicates that Hedgehog (Hh) signaling is activated in human OA and murine models of OA (Lin et al., 2009, Nature Medicine). To identify Hh target genes, microarray analyses were performed to detect changes in gene expression when the Hh pathway was inhibited in human OA cartilage samples.
Regulation of Cholesterol Homeostasis by Hedgehog Signaling in Osteoarthritic Cartilage.
Sex, Specimen part, Treatment
View SamplesWe are currently studying the mechanisms that confer tumour initiating potential upon SP, and as part of this work, we undertook gene profiling studies comparing expression between SP and non-SP cells, initially focusing on the most common soft tissue sarcoma, malignant fibrous histiocytoma (or MFH)
Hedgehog and Notch signaling regulate self-renewal of undifferentiated pleomorphic sarcomas.
No sample metadata fields
View SamplesTumours contain heterogeneous cell populations. A population enriched in tumour-initiating potential has been identified in soft-tissue sarcoma (STS) by the isolation of side population (SP) cells. In this study, we compared the gene expression profiles of SP and non-SP cells in STS and identified Hedgehog (Hh) and Notch pathways as potential candidates for the targeting of SP cells. Upon verification of the activation of these pathways in SP cells, using primary tumor xenografts in NOD-SCID mice as our experimental model, we used the Hh blocker Triparanol and the Notch blocker DAPT to demonstrate that the suppression of these pathways effectively depleted the abundance of SP cells, reduced tumour growth, and inhibited the tumour-initiating potential of the treated sarcoma cells upon secondary transplantation. The data provide additional evidence that SP cells act as tumour initiating cells and points to Hh and Notch pathways as enticing targets for developing potential cancer therapies.
Hedgehog and Notch signaling regulate self-renewal of undifferentiated pleomorphic sarcomas.
Specimen part
View SamplesWe demonstrated that deletion of the p53 tumor suppressor gene in NG2 expressing cells resulted in the development of bone and soft tissue sarcomas that closely resemble human tumors. To determine gene expression differences between NG2 expressing pericytes lacking p53 and sarcomas that arose from deletion of p53 in NG2 expressing cells, RNA sequencing analysis was implemented. Overall design: We isolated total RNA from NG2 expressing pericytes (2 samples), which were sorted from skeletal muscle tissues of NG2-Cre;p53flox/flox mice using an NG2 antibody. We also isolated total RNA from osteosarcomas (2 samples) and soft tissue sarcomas (2 samples), which were developed in NG2-Cre;p53flox/flox mice. Differentially expressed genes were analyzed using Illumina HiSeq 2000.
Mesenchymal Tumors Can Derive from Ng2/Cspg4-Expressing Pericytes with β-Catenin Modulating the Neoplastic Phenotype.
No sample metadata fields
View SamplesCritical disease caused by the new 2009 pandemic influenza virus (nvH1N1) is a challenge for physicians and scientist. As evidenced in SARS and H5N1, the development of an effective immune response plays a key role to overcome viral diseases. We studied host`s gene expression signatures, cytokine and antibody responses along the first week of hospitalization in 19 critically ill patients with primary nvH1N1 pneumonia and two degrees of respiratory involvement. Presence of comorbidities and absence of immunosuppresory conditions were the common antecedents in both groups. The most severe patients (n=12) showed persistant respiratory viral secretion, increased levels of pro-inflammatory cytokines and chemokines in serum, and elevated systemic levels of two immunosuppresory cytokines (IL-10 and IL-1ra). Both groups were able to produce specific antibodies against the virus. The average day for antibody production was day 9 in the course of the disease, defining an early period of innate immunity and a late period of adaptive immunity. The most severe group evidenced a poor expression of a set of MHC class II and T cell receptor (TCR) related genes participating in antigen presentation and cell mediated immune responses in the late phase. 7 patients of this group finally died. This findings evidence that, as observed in sepsis, severe H1N1 disease course with immunoparalysis, which could explain the poor control of the virus along with the increased incidence of bacterial superinfection observed in these patients.
Host adaptive immunity deficiency in severe pandemic influenza.
Specimen part, Subject
View SamplesPURPOSE: Despite over 70,000 new cases of bladder cancer in the United States annually, patients with advanced disease have a poor prognosis due to limited treatment modalities. We evaluate the role of Aurora A, identified as an upregulated candidate molecule in bladder cancer, in regulating bladder tumor growth.
The investigational Aurora kinase A inhibitor MLN8237 induces defects in cell viability and cell-cycle progression in malignant bladder cancer cells in vitro and in vivo.
Specimen part
View SamplesTranscriptome analysis of hindlimb muscles from dystrophic mice
Comparative transcriptome analysis of muscular dystrophy models Large(myd), Dmd(mdx)/Large(myd) and Dmd(mdx): what makes them different?
Sex, Specimen part
View SamplesHow the various cell-types of the body achieve their specific shapes is fundamentally unknown. Here, we explore this issue by identifying genes involved in the elaboration of the complex, yet conserved, cellular morphology of Müller glial (MG) cells in the retina. Using genomic based strategies in zebrafish, we found more than 40 candidate genes involved in specific aspects of MG morphogenesis. The successive steps of cell morphogenesis correlate with the timing of the expression of cohorts of inter-related genes that have roles in generating the particular anatomical features of these cells, suggesting that a sequence of genetic regulomes govern stepwise cellular morphogenesis in this system. Overall design: 12 samples with three replicates each are provided. GFAP:GFP positive and negative cells were FAC sorted from wild type animals from each developmental stage
Genetic control of cellular morphogenesis in Müller glia.
Specimen part, Subject
View Samples