Dataset Information

Single-Cell Transcriptomics of Engineered Cardiac Tissues from Patient-Specific Induced Pluripotent Stem Cell-Derived Cardiomyocytes Reveals Abnormal Developmental Trajectory and Intrinsic Contractile Defects in Hypoplastic Right Heart Syndrome

ABSTRACT: Pulmonary atresia with intact ventricular septum (PAIVS) is a subset of hypoplastic right heart syndrome, a form of congenital heart disease (CHD). Genomic studies on PAIVS patients revealed inconclusive genomic variations and polymorphisms and no animal model yet exists for this disease. Hence, we performed single cell RNA-sequencing (scRNA-seq) on PAIVS patient derived human induced pluripotent stem cell cardiomyocytes (hiPSC-CMs) and its bioengineered cardiac tissue constructs (Human cardiac anisotropic sheeet (hCAS) and cardiac tissue strip (hCTS)) to dissect the intrinsic cardiomyocyte defects. Using pseudotime analysis, we identified pro-maturational cues conferred to hiPSC-CMs by hCAS and hCTS and are attenduated in PAIVS. Moerover, we also identified diminished expression of cardiac contractile apparatus genes in PAIVS hiPSC-CMs and hCTS. Our findings reveal intrinsic abnormalities in cardiac contraction and development in PAIVS in the absence of secondary in vivo remodelling.

ORGANISM(S): Homo sapiens

PROVIDER: GSE157157 | GEO | 2020/09/01

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project 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 (IFNβ1), 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 IFNβ1 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. For this experiment, human induced pluripotent stem cell derived cardiomyocytes were infected with coxsackievirus at multiplicity of infection (MOI) of 5 for 8 hours. Cells were treated with and without interferon beta 1 in order to determine if treatment activates antiviral response genes and/or viral clearance pathways. 4 total samples (2 for each condition) were analyzed

Dataset Information

Single-Cell Transcriptomics of Engineered Cardiac Tissues from Patient-Specific Induced Pluripotent Stem Cell-Derived Cardiomyocytes Reveals Abnormal Developmental Trajectory and Intrinsic Contractile Defects in Hypoplastic Right Heart Syndrome

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets