Uniparental parthenotes are considered an unwanted byproduct of in vitro fertilization. In utero parthenote development is severely compromised by defective organogenesis and in particular by defective cardiogenesis. Although developmentally compromised, apparently pluripotent stem cells can be derived from parthenogenetic blastocysts. Here we hypothesized that nonembryonic parthenogenetic stem cells (PSCs) can be directed toward the cardiac lineage and applied to tissue-engineered heart repair. We first confirmed similar fundamental properties in murine PSCs and embryonic stem cells (ESCs), despite notable differences in genetic (allelic variability) and epigenetic (differential imprinting) characteristics. Haploidentity of major histocompatibility complexes (MHCs) in PSCs is particularly attractive for allogeneic cell-based therapies. Accordingly, we confirmed acceptance of PSCs in MHC-matched allotransplantation. Cardiomyocyte derivation from PSCs and ESCs was equally effective. The use of cardiomyocyte-restricted GFP enabled cell sorting and documentation of advanced structural and functional maturation in vitro and in vivo. This included seamless electrical integration of PSC-derived cardiomyocytes into recipient myocardium. Finally, we enriched cardiomyocytes to facilitate engineering of force-generating myocardium and demonstrated the utility of this technique in enhancing regional myocardial function after myocardial infarction. Collectively, our data demonstrate pluripotency, with unrestricted cardiogenicity in PSCs, and introduce this unique cell type as an attractive source for tissue-engineered heart repair.
Parthenogenetic stem cells for tissue-engineered heart repair.
Specimen part
View SamplesES cells are able to self-renew and remain pluripotent. These characteristics are maintained by both genetic and epigenetic regulators. Protein arginine methyltransferase (PRMT) 4 and 5 are shown to be important in early embryonic development and in ES cells. PRMT6-mediated di-methylation of histone H3 at arginine 2 (H3R2me2) can antagonize the tri-methylation of histone H3 at lysine 4, which marks active genes. However, it is unclear whether PRMT6 and PRMT6-mediated H3R2me2 play crucial roles in early embryonic development and ES cell identity. In this study, we investigate their functions using mouse ES cells as the model.
Protein arginine methyltransferase 6 regulates embryonic stem cell identity.
Cell line
View SamplesExpression profiling of Xenografts of Hepatocellular Carcinoma
Bevacizumab and rapamycin induce growth suppression in mouse models of hepatocellular carcinoma.
Specimen part
View SamplesPurpose: The management of adrenocortical tumors (ACTs) is complex, compounded by the difficulty in discriminating benign from malignant tumors using conventional histology. The Weiss score is the current most widely used system for ACT diagnosis but it has limitations, particularly with ACTs with a score of 3. The am of this study was to identify molecular markers whose expression can discriminate adrenocortical carcinomas (ACCs) from adrenocortical adenomas (ACAs) by microarray gene expression profiling and to determine their clinical applicability by using immunohistochemistry (IHC). Experimental design: Microarray gene expression profiling was used to identify 7 molecular markers which were significantly differentially expressed between ACCs and ACAs. These results were confirmed with quantitative PCR for all 7 genes and IHC for 3 protein. Results: Microarray gene expression profiling was able to accurately categorize ACTs into ACCs and ACAs. All 7 genes were strong discriminators of ACCs from ACAs on qPCR. IHC with IGF2, MAD2L1, CCNB1 and Ki-67, but not ACADVL or ALOX15B, had high diagnostic accuracy in differentiating ACCs from ACAs. The best results however were obtained with a combination of IGF2 and Ki-67 with 96% sensitivity and 100% specificity in diagnosing ACCs. Conclusion: Microarray gene expression profiling accurately differentiates ACCs from ACAs. The combination of IGF2 and Ki-67 IHC is also highly accurate in distinguishing between the 2 groups and is particularly helpful in ACTs with Weiss score of 3.
Microarray gene expression and immunohistochemistry analyses of adrenocortical tumors identify IGF2 and Ki-67 as useful in differentiating carcinomas from adenomas.
No sample metadata fields
View SamplesA distinct type of macrophages helps breast cancer cells to overcome rate-limiting steps in the metastatic process and establish lethal metastatic tumors. Since only a minor population of cancer cells can establish macroscopic metastatic tumors, we hypothesized that this metastatic cancer cell population have higher expression of receptors for macrophage-derived ligands compared to their parental cells.
Mammary Tumor Cells with High Metastatic Potential Are Hypersensitive to Macrophage-Derived HGF.
Specimen part
View SamplesWe are investigating the transcriptional response of newborns in response to prenatal arsenic exposure
Activation of inflammation/NF-kappaB signaling in infants born to arsenic-exposed mothers.
No sample metadata fields
View SamplesThe transcriptional effects of urocortin I, urocortin II and tempol were compared to saline treatment in a rat model of in vivo coronary artery occlusion model of ischaemia/reperfusion injury of 25 min ischaemia and 2 hr reperfusion. <br></br>The treatment groups were as follows (i) sham operation or LAD occlusion with infusion of (ii) saline, (iii) 15 ?g/kg Ucn I, (iv) 15 ?g/kg Ucn II and (v) 100 mg/kg tempo infused just prior to reperfusionl.<br></br>Following 2 hr reperfusion the left ventricle was removed, snap frozen, followed by RNA extraction.
New targets of urocortin-mediated cardioprotection.
Sex, Age, Specimen part, Disease, Disease stage, Subject, Compound, Time
View SamplesEpithelial-mesenchymal transition (EMT) induced by microenvironment stimuli can be attributed to the transcriptional regulation of epithelial and mesenchymal phenotypes. Here we show how EMT is coordinated with cancer metabolism, an emerging hallmark of tumorigenesis.
Targeting metabolic flexibility via angiopoietin-like 4 protein sensitizes metastatic cancer cells to chemotherapy drugs.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Epstein-Barr virus-associated primary nodal T/NK-cell lymphoma shows a distinct molecular signature and copy number changes.
Disease, Disease stage
View SamplesTo investigate if biologically distinct subsets exists in extranodal NK/T-cell lymphoma (NKTL), we performed unsupervised integrative analyses of gene expression profiling (GEP), miRNA profiling, and copy number aberration (CNA) on 66 cases of NKTL from diverse anatomical sites. This series is the GEP data.
Epstein-Barr virus-associated primary nodal T/NK-cell lymphoma shows a distinct molecular signature and copy number changes.
Disease, Disease stage
View Samples