The availability of pluripotent stem cells offers the possibility of using such cells to model hepatic disease and development. With this in mind, we previously established a protocol that facilitates the differentiation of both human embryonic stem cells and induced pluritpotent cells into cells with hepatocyte characteristics. The use of highly defined culture conditions and the avoidance of feeder cells or embryoid bodies allowed synchronous and reproducible differentiation to occur. The differentiation toward a hepatocytelike fate appeared to recapitulate many of the stages normally associated with the formation of hepatocytes in vivo. In the current study we addressed the feasibility of using human pluripotent stem cells to probe the molecular mechanisms underlying human hepatocyte differentiation. We demonstrate i) that human ES cells express a number of mRNAs that characterize each stage in the differentiation process, ii) that gene expression can be efficiently depleted throughout the differentiation time course using shRNAs expressed from lentiviruses, and iii) that the nuclear hormone receptor HNF4a is essential for specification of human hepatic progenitor cells by establishing expression of the network of transcription factors that control hepatocyte cell fate.
HNF4A is essential for specification of hepatic progenitors from human pluripotent stem cells.
Specimen part, Time
View SamplesQuantitative assays for human DNA and mRNA were used to examine the paradox that intravenously (IV) infused human multipotent stromal cells (hMSCs) can enhance tissue repair without significant engraftment. After 2 X 106 hMSCs were IV infused into mice, most of the cells were trapped as emboli in lung. The cells in lung disappeared with a half-life of about 24 hr but < 1,000 cells appeared in 6 other tissues. The hMSCs in lung up-regulated expression of multiple genes with a large increase in the anti-inflammatory protein TSG-6. After myocardial infarction, IV hMSCs but not hMSCs transduced with TSG-6 siRNA decreased inflammatory responses, reduced infarct size, and improved cardiac function. IV administration of recombinant TSG-6 also reduced inflammatory responses and reduced infarct size. The results suggest improvements in animal models and patients after IV infusions of MSCs are at least in part explained by activation of MSCs to secrete TSG-6.
Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6.
Specimen part, Disease
View SamplesThe cellular origin of Ewing tumor (ET), a tumor of bone or soft tissues characterized by specific fusions between EWS and ETS genes, is highly debated. Through gene expression analysis comparing ETs with a variety of normal tissues, we show that the profiles of different EWS-FLI1-silenced Ewing cell lines converge toward that of mesenchymal stem cells (MSC). Moreover, upon EWS-FLI1 silencing, two different Ewing cell lines can differentiate along the adipogenic lineage when incubated in appropriate differentiation cocktails. In addition, Ewing cells can also differentiate along the osteogenic lineage upon long-term inhibition of EWS-FLI1. These in silico and experimental data strongly suggest that the inhibition of EWS-FLI1 may allow Ewing cells to recover the phenotype of their MSC progenitor.
Mesenchymal stem cell features of Ewing tumors.
Specimen part
View SamplesWe sequenced mRNA from two preparations of isolated Notch-responsive ductal pancreas cells and compared transcript expression to all other non-Notch-responsive cells from each sample to charactarize zebrafish centroacinar cells. Overall design: Determination of gene expression levels in centroacinar cells and non-centroacinar cells from adult pancreas.
Centroacinar Cells Are Progenitors That Contribute to Endocrine Pancreas Regeneration.
No sample metadata fields
View SamplesThis study was designed to investigate the transcripts that are regulated by Twist1 in skin tymor epithelial cells in a p53-dependent and independent manner. To this aim, Tumor epithelial cells from primary mouse skin tumors of different genotypes were FACS sorted and analyzed by microarray.
Different levels of Twist1 regulate skin tumor initiation, stemness, and progression.
Specimen part, Treatment
View SamplesPolycomb-group proteins form multimeric protein complexes involved in transcriptional silencing. The Polycomb Repressive complex 2 (PRC2) contains the Suppressor of Zeste-12 protein (Suz12) and the histone methyltransferase Enhancer of Zeste protein-2 (Ezh2). This complex, catalyzing the di- and tri-methylation of histone H3 lysine 27, is essential for embryonic development and stem cell renewal. However, the role of Polycomb-group protein complexes in the control of the intestinal epithelial cell (IEC) phenotype is not known. We investigated the impact of Suz 12 depletion on gene expression in IEC-6 cells.
The histone H3K27 methylation mark regulates intestinal epithelial cell density-dependent proliferation and the inflammatory response.
Cell line
View SamplesDespite advances in Hodgkin lymphoma (HL) treatment, about 20% of patients still die due to progressive disease. Current prognostic models predict treatment outcome with imperfect accuracy, and clinically relevant biomarkers are yet to be established that improve upon the International Prognostic Scoring (IPS) system. We analyzed 130 frozen diagnostic lymph node biopsies from classical HL patients by gene expression profiling to describe cellular signatures correlated with treatment outcome.
Tumor-associated macrophages and survival in classic Hodgkin's lymphoma.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesThe C57BL/6.NOD-Aec1Aec2 mouse is a model for primary Sjgrens syndrome and was constructed by introducing two genetic intervals derived from the NOD mouse that confers Sjgrens syndrome (SjS)-like disease in SjS-non-susceptible C57BL/6 mice.
Transcriptional landscapes of emerging autoimmunity: transient aberrations in the targeted tissue's extracellular milieu precede immune responses in Sjögren's syndrome.
Sex, Age, Specimen part
View SamplesWe generated gene expression profiles of N2 (wild type) and strain FAS43 (Histone H3.3 null worms containing knockout alleles of all genes with homology to human histone H3.3: his-69, his-70, his-71, his-72, his-74) at embryonic and first larval instar stages. Overall design: RNA was isolated from N2 and H3.3 null mixed-stage embryos and L1 larvae grown at 20°C using Trizol, in duplicates for all samples. RNA-seq libraries were prepared using the Illumina TruSeq protocol.
Differential Expression of Histone H3.3 Genes and Their Role in Modulating Temperature Stress Response in <i>Caenorhabditis elegans</i>.
Cell line, Subject
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Sox9 Controls Self-Renewal of Oncogene Targeted Cells and Links Tumor Initiation and Invasion.
Specimen part
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