17beta-hydroxysteroid dehydrogenase type12 (HSD17B12) has been demonstrated to be involved in regulation of in situ biosynthesis of estradiol (E2). HSD17B12 expression was reported in breast carcinomas but its functions have remained unknown. Therefore, we examined the correlation between mRNA expression profiles determined by microarray analysis and tissue E2 concentrations obtained from 16 postmenopausal breast carcinoma cases in order to analyze an association of the enzyme expression with intratumoral E2 production. No significant correlations were detected between intratumoral HSD17B12expression and E2 concentration.These findings suggest that the presence of HSD17B12 in carcinoma cells contributes to a development of human breast carcinoma via a pathway other than in situ E2 biosynthesis.
17Beta-hydroxysteroid dehydrogenase type 12 in human breast carcinoma: a prognostic factor via potential regulation of fatty acid synthesis.
Sex, Specimen part
View SamplesDrug-induced cardiac arrhythmia characterized by QT prolongation and torsade de pointes has been a major reason for drug withdrawal at the late stage of clinical trials. Current preclinical testing is still insufficient to identify drugs with pro-arrhythmic risks. Human induced pluripotent stem cell-derived cardiomyocytes are a promising development in safety screening as a reproducible human model. Using the patch-clamp technique, we showed that human induced pluripotent stem cell-derived cardiomyocytes exhibited spontaneous action potentials, which represent relatively immature forms of cardiac cells. Furthermore, in some spontaneously beating cells, a hERG blocker, E4031, depolarized membrane potentials and stopped spontaneous firing, resulting in failure to evaluate drug effects on electrophysiological parameters that reflect repolarization processes. Here we show that human stem cell-derived cardiomyocytes with transduced KCNJ2 encoding the inward-rectifier potassium channel have characteristics similar to mature cardiomyocytes including responsiveness to rate changes and potassium channel blockers. Our novel strategy could allow implementation of human induced pluripotent stem cell-derived cardiomyocytes in drug safety assessment for cardiac toxicity.
Overexpression of KCNJ2 in induced pluripotent stem cell-derived cardiomyocytes for the assessment of QT-prolonging drugs.
Specimen part
View SamplesMre11, together with Rad50 and Xrs2/NBS, plays pivotal roles in homologous recombination, repair of DNA double strand breaks (DSBs), activation of damage-induced checkpoint, and telomere maintenance. Using DNA microarray assays to analyze yeast mutants (mre11delta, rad50delta, and spo11Y135F) defective for meiotic DSB formation, we demonstrate that the absence of Mre11 in yeast causes specific effects on regulation of a class of meiotic genes for spore development. The transcriptional deficiency was not observed in other DSB mutants such as rad50delta and spo11Y135F, suggesting the transcriptional defect in mre11delta is due to neither lack of meiotic DSB formation, nor disintegrity of Mre11-Rad50-Xrs2 complex.These defects were confirmed by northern and lacZ reporter gene assays.
Mre11 mediates gene regulation in yeast spore development.
No sample metadata fields
View SamplesTo identify molecular pathological alterations in AD brains, we performed interspecies comparative microarray analyses using RNAs prepared from postmortem human brain tissues donated for the Hisayama study and hippocampal RNAs from the triple-transgenic mouse model of AD (3xTg-AD)
Altered expression of diabetes-related genes in Alzheimer's disease brains: the Hisayama study.
Sex, Age, Specimen part
View SamplesTo identify molecular pathological alterations in AD brains, we performed interspecies comparative microarray analyses using RNAs prepared from postmortem human brain tissues donated for the Hisayama study and hippocampal RNAs from the triple-transgenic mouse model of AD (3xTg-AD)
Altered expression of diabetes-related genes in Alzheimer's disease brains: the Hisayama study.
Sex, Age, Specimen part
View SamplesGeneChip-based screen for genes induced in the initial phase of neural differentiation from ES cells.
Intrinsic transition of embryonic stem-cell differentiation into neural progenitors.
No sample metadata fields
View SamplesComparison of wild type barley plants versus plants over-expressing ODDSOC2; a vernalization responsive MADS box gene ****[PLEXdb(http://www.plexdb.org) has submitted this series at GEO on behalf of the original contributor, Aaron Greenup. The equivalent experiment is BB93 at PLEXdb.]
ODDSOC2 is a MADS box floral repressor that is down-regulated by vernalization in temperate cereals.
Specimen part
View SamplesRegulation of organ size is important for development and tissue homeostasis. In Drosophila, Hippo signaling controls organ size by regulating the activity of a TEAD transcription factor, Scalloped, through modulation of its coactivator protein Yki. The role of mammalian Tead proteins in growth regulation, however, remains unknown. Here we examined the role of mouse Tead proteins in growth regulation. In NIH3T3 cells, cell density and Hippo signaling regulated the activity of Tead proteins by modulating nuclear localization of a Yki homologue, Yap, and the resulting change in Tead activity altered cell proliferation. Tead2-VP16 mimicked Yap overexpression, including increased cell proliferation, reduced cell death, promotion of EMT, lack of cell contact inhibition, and promotion of tumor formation. Growth promoting activities of various Yap mutants correlated with their Tead-coactivator activities. Tead2-VP16 and Yap regulated largely overlapping sets of genes. However, only a few of the Tead/Yapregulated genes in NIH3T3 cells were affected in Tead1-/-;Tead2-/- or Yap-/- embryos. Most of the previously identified Yap-regulated genes were not affected in NIH3T3 cells or mutant mice. In embryos, levels of nuclear Yap and Tead1 varied depending on cell types. Strong nuclear accumulation of Yap and Tead1 were seen in myocardium, correlating with requirements of Tead1 for proliferation. However, their distribution did not always correlate with proliferation. Taken together, mammalian Tead proteins regulate cell proliferation and contact inhibition as a transcriptional mediator of Hippo signaling, but the mechanisms by which Tead/Yap regulate cell proliferation differ depending on cell types, and Tead, Yap and Hippo signaling may play multiple roles in mouse embryos.
Mammalian Tead proteins regulate cell proliferation and contact inhibition as transcriptional mediators of Hippo signaling.
No sample metadata fields
View SamplesHuman embryonic stem cells (hESCs) have the unique property of immortality, ability to infinitely self-renew and survive in vitro. In contrast to tumor-deribed cells, their immortality are free from any genomic abberations. Instead, they depend on the AKAP-Lbc/Rho signaling cascade. To understand the downstream way, we performed RNA-seq analyses between normal and AKAP-Lbc-depleted hESCs using the doxycyclin-inducible gene silensing strategy. Overall design: We use the genetically modified hESCs in which AKAP-13-targeting shRNA is induced by doxycyclin(dox) treatment. To minimize cell loss during treatment, anti-apoptotic factor Bcl-XL is overexpressed. We collected RNA from dox-treated and untreated cells in biological triplicate. We measured gene expression in these 2 sample groups using RNA-seq (illumina HiSeq) .
Rho-Signaling-Directed YAP/TAZ Activity Underlies the Long-Term Survival and Expansion of Human Embryonic Stem Cells.
No sample metadata fields
View SamplesGenome instability is a potential limitation to the research and therapeutic application of induced pluripotent stem cells (iPSCs). Observed genomic variations reflect the combined activities of DNA damage, cellular DNA damage response (DDR), and selection pressure in culture. To understand the contribution of DDR on the distribution of copy number variations (CNVs) in iPSCs, we mapped CNVs of iPSCs with mutations in the central DDR gene ATM onto genome organization landscapes defined by genome-wide replication timing profiles. We show that following reprogramming the early and late replicating genome is differentially affected by CNVs in ATM deficient iPSCs relative to wild type iPSCs. Specifically, the early replicating regions had increased CNV losses during retroviral reprogramming. This differential CNV distribution was not present after later passage or after episomal reprogramming. Comparison of different reprogramming methods in the setting of defective DNA damage response reveals unique vulnerability of early replicating open chromatin to retroviral vectors.
Influence of ATM-Mediated DNA Damage Response on Genomic Variation in Human Induced Pluripotent Stem Cells.
Specimen part
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