Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA285162 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Nos3-/- iPSCs model concordant signatures of in utero cardiac pathogenesis [iPSCs]
| PRJNA285161 | ENA
Project description:Nos3-/- iPSCs model concordant signatures of in utero cardiac pathogenesis
| PRJNA285157 | ENA
Project description:Through genome-wide transcriptional comparisons, this study interrogates the capacity of iPSCs to accurately model pathogenic signatures of structural cardiac defects. Herein, we studied the molecular etiology of structural cardiac defects in Nos3-/- mice via transcriptional analysis of stage-matched embryonic and iPSC-derived tissues. In vitro comparisons of differentiated embryoid bodies were calibrated to in utero benchmarks of health and disease. Integrated systems biology analysis of WT and Nos3-/- transcriptional profiles revealed 50% concordant expression patterns between in utero embryonic and ex vivo iPSC-derived tissue. In particular, up-regulation of glucose metabolism (p-value = 3.95x10-12) and down-regulation of fatty acid metabolism (p-value = 6.71x10-12) highlight a bioenergetic signature of early Nos3 deficiency during cardiogenesis that can be recapitulated in iPSC-derived tissues. The in vitro concordance of early Nos3-/- disease signatures supports the utility of iPSCs as a cell-autonomous model of structural heart defects. Moreover, this study supports the use of iPSCs as a platform to pinpoint initial stages of cardiac pathogenesis.
2015-09-27 | GSE69316 | GEO
Project description:Through genome-wide transcriptional comparisons, this study interrogates the capacity of iPSCs to accurately model pathogenic signatures of structural cardiac defects. Herein, we studied the molecular etiology of structural cardiac defects in Nos3-/- mice via transcriptional analysis of stage-matched embryonic and iPSC-derived tissues. In vitro comparisons of differentiated embryoid bodies were calibrated to in utero benchmarks of health and disease. Integrated systems biology analysis of WT and Nos3-/- transcriptional profiles revealed 50% concordant expression patterns between in utero embryonic and ex vivo iPSC-derived tissue. In particular, up-regulation of glucose metabolism (p-value = 3.95x10-12) and down-regulation of fatty acid metabolism (p-value = 6.71x10-12) highlight a bioenergetic signature of early Nos3 deficiency during cardiogenesis that can be recapitulated in iPSC-derived tissues. The in vitro concordance of early Nos3-/- disease signatures supports the utility of iPSCs as a cell-autonomous model of structural heart defects. Moreover, this study supports the use of iPSCs as a platform to pinpoint initial stages of cardiac pathogenesis.
2015-09-27 | GSE69315 | GEO
Project description:Congenital heart disease (CHD) is the most common type of birth defect, affecting ~1% of all live births. Malformations of the cardiac outflow tract (OFT) account for ~30% of all CHD and include a range of CHDs from bicuspid aortic valve (BAV) to tetralogy of Fallot (TOF). We hypothesized that transcriptomic profiling of a mouse model of CHD would highlight disease-contributing genes implicated in congenital cardiac malformations in humans. To test this hypothesis, we utilized global transcriptional profiling differences from a mouse model of OFT malformations to prioritize damaging, de novo variants identified from exome sequencing datasets from published cohorts of CHD patients. Notch1+/-;Nos3-/- mice display a spectrum of cardiac OFT malformations ranging from BAV, semilunar valve (SLV) stenosis to TOF. Global transcriptional profiling of the E13.5 Notch1+/-;Nos3-/- mutant mouse OFTs and wildtype controls was performed by RNA sequencing (RNA-Seq). Analysis of the RNA-Seq dataset demonstrated genes belonging to the Hif1α, Tgf-β, Hippo, and Wnt signaling pathways were differentially expressed in the mutant OFT. Mouse to human comparative analysis was then performed to determine if patients with TOF and SLV stenosis display an increased burden of damaging, genetic variants in gene homologs that were dysregulated in Notch1+/-; Nos3-/- OFT. We found an enrichment of de novo variants in the TOF population among the 1,352 significantly differentially expressed genes in Notch1+/-;Nos3-/- mouse OFT but not the SLV population. This association was not significant when compared to only highly expressed genes in the murine OFT and of de novo variants in the TOF population. These results suggest that transcriptomic datasets generated from the appropriate temporal, anatomic and cellular tissues from murine models of CHD may provide a novel approach for the prioritization of disease-contributing genes in patients with CHD.
2021-06-28 | GSE171238 | GEO
Project description:Congenital heart disease (CHD) is the most common type of birth defect, affecting ~1% of all live births. Malformations of the cardiac outflow tract (OFT) account for ~30% of all CHD and include a range of CHDs from bicuspid aortic valve (BAV) to tetralogy of Fallot (TOF). We hypothesized that transcriptomic profiling of a mouse model of CHD would highlight disease-contributing genes implicated in congenital cardiac malformations in humans. To test this hypothesis, we utilized global transcriptional profiling differences from a mouse model of OFT malformations to prioritize damaging, de novo variants identified from exome sequencing datasets from published cohorts of CHD patients. Notch1+/-;Nos3-/- mice display a spectrum of cardiac OFT malformations ranging from BAV, semilunar valve (SLV) stenosis to TOF. Global transcriptional profiling of the E13.5 Notch1+/-;Nos3-/- mutant mouse OFTs and wildtype controls was performed by RNA sequencing (RNA-Seq). Analysis of the RNA-Seq dataset demonstrated genes belonging to the Hif1α, Tgf-β, Hippo, and Wnt signaling pathways were differentially expressed in the mutant OFT. Mouse to human comparative analysis was then performed to determine if patients with TOF and SLV stenosis display an increased burden of damaging, genetic variants in gene homologs that were dysregulated in Notch1+/-; Nos3-/- OFT. We found an enrichment of de novo variants in the TOF population among the 1,352 significantly differentially expressed genes in Notch1+/-;Nos3-/- mouse OFT but not the SLV population. This association was not significant when compared to only highly expressed genes in the murine OFT and of de novo variants in the TOF population. These results suggest that transcriptomic datasets generated from the appropriate temporal, anatomic and cellular tissues from murine models of CHD may provide a novel approach for the prioritization of disease-contributing genes in patients with CHD.
2021-06-28 | GSE171237 | GEO
Project description:microRNA signatures of iPSCs and endoderm-derived tissues
| PRJNA151775 | ENA
Project description:We set up a 3D model based on iPSCs derived from patients with familial forms of Alzheimer’s disease (AD) and healthy non-demented control. We created cerebral organoids (COs), verified their ability to mimic AD in vitro, and used it to explore early events and the progression of AD pathogenesis. Our data reveal that despite similar expression of cell-type-specific genes during CO maturation in vitro, AD-iPSCs derived COs show limited tissue patterning and altered cellular development. These findings complement unique single-cell sequencing data of AD-iPSCs derived COs confirming this observation and uncovering that a sub-set of neurons in AD-iPSCs likely differentiates prematurely while at the same time retaining the expression of progenitor marker PAX6.
2022-07-01 | E-MTAB-11438 | biostudies-arrayexpress
Project description:The fact that Parkinsons disease (PD) can arise from numerous genetic mutations suggests a unifying molecular pathology underlying the various genetic backgrounds. In order to address this hypothesis, an integrated approach utilizing in vitro disease modeling and comprehensive transcriptome profiling was taken to advance our understanding of PD progression and the concordant downstream signaling pathways across divergent genetic predispositions. To model PD in vitro, neurons harboring disease-causing mutations were generated from patient-specific, induced pluripotent stem cells (iPSCs) and found to recapitulate several disease-related phenotypes. Signs of degeneration in PD midbrain dopaminergic (mDA) neurons were observed, reflecting the cardinal feature of PD. In addition, novel gene expression signatures were revealed for PD mDA neurons, providing molecular insights to disease phenotype observed in vitro, including oxidative stress vulnerability and altered neuronal activity. Notably, detailed transcriptome profiling of PD neurons showed that elevated RBFOX1, a gene previously linked to neurodevelopmental diseases, is responsible for a pattern of alternative RNA processing associated with PD-specific phenotypes in vitro.
2016-06-07 | E-MTAB-4586 | biostudies-arrayexpress
Project description:Abstract: Although COVID-19–associated heart dysfunction has identified in individuals with SARS-CoV-2 infection, complex and multifaceted pathophysiology in patients complicates the investigation of pathogenesis related to clinical manifestations and mechanisms of cardiac dysfunction after viral invasion. This study comprehensively investigated pathogenesis regarding SARS-CoV-2 infection via tissue model established from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and cardiomyopathy model induced by angiotensin II. We recapitulated cytopathic features of SARS-CoV-2-induced cardiac damage and monitored the course of cardiac complications after infection, which is critically important to develop therapeutics. We found that SARS-CoV-2 infection of hiPSC-CMs models progressively impaired contractile function and calcium handling and led to cell death. Therapeutics potential towards myocardial injury was further developed in our tissue model. We evaluated cardioprotective effects of extracellular vesicles (EVs) derived from hiPSC source on the infected tissues, indicating that EVs alleviated the impairment of contractile force and cardiac cell death following SARS-CoV-2 infection. We showed that enriched microRNA in hiPSC-EVs can modulate cardiac-specific processes. These findings suggested that cardiac manifestations examined from tissues models provided insights into cardiac injury induced by SARS-CoV-2 infection, and model systems allow the investigation of mechanisms driving cardiac dysfunction and iPSC-EVs served as a promising therapy to rescue cardiac damage from infection.
2022-04-09 | GSE185602 | GEO