Filters
Technology
Platform
GSE37896
Homo sapiens
7 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Baseline gene expression of adipose stem cell derived iPSCs generated by lentiviral Yamanaka 4 factors. We used microarrays to analyze the global gene expression of hACS derived iPSCs with KMOS and KMOS+miR-302.
Publication Title
MicroRNA-302 increases reprogramming efficiency via repression of NR2F2.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Little is known about the function of induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) generated from diabetics, as this could potentially limit subsequent therapeutic use in this patient population.
Publication Title
Pravastatin reverses obesity-induced dysfunction of induced pluripotent stem cell-derived endothelial cells via a nitric oxide-dependent mechanism.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
IlluminaHiSeq2000
Description
We investigated the ALDH2*2 genetic polymorphism and its underlying mechanisms for the first time in a human model system of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) generated from individuals carrying the most common heterozygous form of the ALDH2*2 genotype. We showed that the ALDH2*2 mutation confers elevated levels of reactive oxygen species (ROS) and toxic aldehydes such as 4HNE, thereby inducing cell cycle arrest and activation of apoptotic signaling pathways, especially during ischemic injury. ALDH2 exerts control of cell survival decisions via modulation of oxidative stress levels. This regulatory circuitry was found to be dysfunctional in the loss-of-function ALDH2*2 genotype, causing upregulation of apoptosis in cardiomyocytes following ischemic insult. These results reveal a novel function of the metabolic enzyme ALDH2 in modulation of cell survival decisions. Overall design: Molecular mechanism of increased ischemic damage in cardiomyocytes of ALDH2*2 genotype.
Publication Title
Characterization of the molecular mechanisms underlying increased ischemic damage in the aldehyde dehydrogenase 2 genetic polymorphism using a human induced pluripotent stem cell model system.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- IlluminaHiSeq2000
Description
Doxorubicin (Adriamycin) is an anthracycline chemotherapy agent effective in treating a wide range of malignancies1 with a well-established dose-response cardiotoxic side-effect that can lead to heart failure2-4. Even at relatively low cumulative doses of 200–250 mg/m2, the risk of cardiotoxicity is estimated at 7.8% to 8.8%4,5. Doxorubicin-induced cardiotoxicity (DIC) can range from asymptomatic reductions in left ventricular ejection fraction (LVEF) to highly symptomatic heart failure6,7. At present, it is not possible to predict which patients will be affected by DIC or adequately protect patients who are at risk for suffering this devastating side-effect8. Here we demonstrate that patient-specific human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) can recapitulate individual patients’ predilection to DIC at the single cell level. hiPSC-CMs derived from breast cancer patients who suffered clinical DIC are consistently more sensitive to doxorubicin toxicity, demonstrating decreased cell viability, mitochondrial/metabolic function, calcium handling, and antioxidant pathway gene expression, along with increased reactive oxygen species (ROS) production compared to hiPSC-CMs from patients who did not experience DIC. Together, our data indicate that hiPSC-CMs are a suitable platform for identifying and verifying the genetic basis and molecular mechanisms of DIC. Overall design: Comparision of the effect of 1uM doxorubicin for 24 h on gene expression in hiPSC-CM derived from 6 patients
Publication Title
Human induced pluripotent stem cell-derived cardiomyocytes recapitulate the predilection of breast cancer patients to doxorubicin-induced cardiotoxicity.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Microarray data on H9 hESC-derived cardiomyocytes (d30) treated with 0, 0.1, 1, or 10 uM of doxorubicin for 24 h
Publication Title
Human induced pluripotent stem cell-derived cardiomyocytes recapitulate the predilection of breast cancer patients to doxorubicin-induced cardiotoxicity.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 1 Downloadable Sample
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
ABSTRACT Background: Viral myocarditis is a life-threatening illness that may lead to heart failure or cardiac arrhythmias. This study examined whether human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) could be used to model the pathogenic processes of coxsackievirus-induced viral myocarditis and to screen antiviral therapeutics for efficacy. Methods and Results: Human iPSC-CMs were infected with a luciferase-expressing mutant of the coxsackievirus B3 strain (CVB3-Luc). Brightfield microscopy, immunofluorescence, and calcium imaging were used to characterize virally infected hiPSC-CMs. Viral proliferation on hiPSC-CMs was subsequently quantified using bioluminescence imaging. For drug screening, select antiviral compounds including interferon beta 1 (IFN1), ribavirin, pyrrolidine dithiocarbamate (PDTC), and fluoxetine were tested for their capacity to abrogate CVB3-Luc proliferation in hiPSC-CMs in vitro. The ability of some of these compounds to reduce CVB3-Luc proliferation in hiPSC-CMs was consistent with the reported drug effects in previous studies. Finally, mechanistic analyses via gene expression profiling of hiPSC-CMs infected with CVB3-Luc revealed an activation of viral RNA and protein clearance pathways within these hiPSC-CMs after IFN1 treatment. Conclusions: This study demonstrates that hiPSC-CMs express the coxsackievirus and adenovirus receptor, are susceptible to coxsackievirus infection, and can be used to confirm antiviral drug efficacy. Our results suggest that the hiPSC-CM/CVB3-Luc assay is a sensitive platform that could be used to screen novel antiviral therapeutics for their effectiveness in a high-throughput fashion.
Publication Title
Human induced pluripotent stem cell-derived cardiomyocytes as an in vitro model for coxsackievirus B3-induced myocarditis and antiviral drug screening platform.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
High-throughput screening of tyrosine kinase inhibitor cardiotoxicity with human induced pluripotent stem cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Tyrosine kinase inhibitors (TKIs), despite efficacy as anti-cancer therapies, are associated with cardiovascular side effects ranging from induced arrhythmias to heart failure. We have utilized patient-specific human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), generated from 11 healthy individuals and 2 patients receiving cancer treatment, to screen FDA-approved TKIs for cardiotoxicities by measuring alterations in cardiomyocyte viability, contractility, electrophysiology, calcium handling, and signaling. With these data, we generated a cardiac safety index to assess cardiotoxicities of existing TKIs. Many TKIs with a low cardiac safety index exhibit cardiotoxicity in patients. We also derived endothelial cells (hiPSC-ECs) and cardiac fibroblasts (hiPSC-CFs) to examine cell type-specific cardiotoxicities. Using high-throughput screening, we determined that VEGFR2/PDGFR-inhibiting TKIs caused cardiotoxicity in hiPSC-CMs, hiPSC-ECs, and hiPSC-CFs. Using phosphoprotein analysis, we determined that VEGFR2/PDGFR-inhibiting TKIs led to a compensatory increase in cardioprotective insulin and insulin-like growth factor (IGF) signaling in hiPSC-CMs. Activating cardioprotective signaling with exogenous insulin or IGF1 improved hiPSC-CM viability during co-treatment with cardiotoxic VEGFR2/PDGFR-inhibiting TKIs. Thus, hiPSC-CMs can be used to screen for cardiovascular toxicities associated with anti-cancer TKIs, correlating with clinical phenotypes. This approach provides unexpected insights, as illustrated by our finding that toxicity can be alleviated via cardioprotective insulin/IGF signaling.
Publication Title
High-throughput screening of tyrosine kinase inhibitor cardiotoxicity with human induced pluripotent stem cells.
Sample Metadata Fields
Treatment, Subject
View Samples- Bos taurus
- 18 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
Selenium (Se) is an essential nutrient for beef cattle health and commercial production. The molecular mechanisms responsible for the physiological responses of the animal to dietary Se supplementation, however, have not been evaluated. Furthermore, the potential effect of two chemical forms (organic vs. inorganic) of Se on gene expression by Se-sufficient cattle has not been evaluated.
Publication Title
Dietary supplementation of selenium in inorganic and organic forms differentially and commonly alters blood and liver selenium concentrations and liver gene expression profiles of growing beef heifers.
Sample Metadata Fields
Specimen part
View Samples- Bos taurus
- 13 Downloadable Samples
- Bovine Gene 1.0 ST Array (bovgene10st)
Description
In many parts of the US, selenium (Se)-deficient soils dictate the necessity of supplementing this trace mineral directly to the diet of cattle, with the form of Se supplied known to affect tissue-level gene expression profiles and presumably function. Because a deficiency of Se will reduce fertility, including reduced biosynthesis of testosterone by the testis and an increased frequency of abnormalities in mature spermatozoa, we hypothesized that the form of Se supplemented to cows during gestation would affect the transcriptome of the neonatal bull calf testis. Microarray analysis using the Bovine gene 1.0 ST array (GeneChip; Affymetrix, Inc., Santa Clara, CA) was conducted to determine whether gestational form of supplemental Se affected gene expression profiles in the testis. GeneChip transcript annotations were last updated in January 2013 using the annotation update release 33 from the NetAffx annotation database.
Publication Title
Gestational form of Selenium in Free-Choice Mineral Mixes Affects Transcriptome Profiles of the Neonatal Calf Testis, Including those of Steroidogenic and Spermatogenic Pathways.
Sample Metadata Fields
Specimen part
View Samples