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.
Pravastatin reverses obesity-induced dysfunction of induced pluripotent stem cell-derived endothelial cells via a nitric oxide-dependent mechanism.
Age, Specimen part
View SamplesWe 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.
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.
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View SamplesABSTRACT 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.
Human induced pluripotent stem cell-derived cardiomyocytes as an in vitro model for coxsackievirus B3-induced myocarditis and antiviral drug screening platform.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Identifying and avoiding off-target effects of RNase H-dependent antisense oligonucleotides in mice.
Sex, Specimen part, Treatment
View SamplesWe used microarrays to globally profile the gene expression changes observed in liver after 3 days when dosing antisense oligonucleotides in mice
Identifying and avoiding off-target effects of RNase H-dependent antisense oligonucleotides in mice.
Sex, Specimen part, Treatment
View SamplesWe used microarrays to globally profile the gene expression changes observed in liver after 3 days when dosing an antisense oligonucleotide in mice
Identifying and avoiding off-target effects of RNase H-dependent antisense oligonucleotides in mice.
Sex, Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Temporal- and strain-specific host microRNA molecular signatures associated with swine-origin H1N1 and avian-origin H7N7 influenza A virus infection.
Cell line
View SamplesMicroRNAs (miRNAs) repress the expression levels of genes by binding to mRNA transcripts, acting as master regulators of cellular processes. Differential expression of miRNAs has been linked to viral-associated diseases involving members of the hepacivirus, herpesvirus, and retrovirus families. In contrast, limited biological and molecular information has been reported on the potential role of cellular miRNAs in the lifecycle of influenza A viruses (infA). In this study, we hypothesize that elucidating the miRNA expression signatures induced by low-pathogenic swine-origin influenza A virus (S-OIV) pandemic H1N1 (2009) and highly pathogenic avian-origin (A-OIV) H7N7 (2003) infections could reveal temporal and strain-specific miRNA fingerprints during the viral lifecycle, shedding important insights into the potential role of cellular miRNAs in host-infA interactions. Using a microfluidic microarray platform, we profiled cellular miRNA expression in human A549 cells infected with S- and A-OIVs at multiple time-points during the viral lifecycle, including global gene expression profiling during S-OIV infection. Using target prediction and pathway enrichment analyses, we identified the key cellular pathways associated with the differentially expressed miRNAs and predicted mRNA targets during infA infection, including immune system, cell proliferation, apoptosis, cell cycle, and DNA replication and repair. By identifying the specific and dynamic molecular phenotypic changes (microRNAome) triggered by S- and A-OIV infection in human cells, we provide experimental evidence demonstrating a series of temporal- and strain-specific host molecular responses involving different combinatorial contributions of multiple cellular miRNAs. Our results also identify novel potential exosomal miRNA biomarkers associated with pandemic S-OIV and deadly A-OIV-host infection.
Temporal- and strain-specific host microRNA molecular signatures associated with swine-origin H1N1 and avian-origin H7N7 influenza A virus infection.
Cell line
View Samples[Hela cells]: We performed cdr2 knockdown with a pool of 4 cdr2-specific siRNAs to test whether cdr2 may regulate c-myc target genes as cells passage through mitosis.
The onconeural antigen cdr2 is a novel APC/C target that acts in mitosis to regulate c-myc target genes in mammalian tumor cells.
Cell line
View SamplesTo characterize the transcriptional program that governs terminal granulocytic differentation in vivo, we performed comprehensive microarray analysis of human bone marrow population highly enriched for promyelocytes, myelocytes / metamyelocytes and neotrophils.
Human neutrophils secrete bioactive paucimannosidic proteins from azurophilic granules into pathogen-infected sputum.
Specimen part
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