Temporal single-cell transcriptomic profiling of cardiac differentiation in pulmonary atresia with intact ventricular septum (PA-IVS) derived induced pluripotent stem cells

Pulmonary atresia with the intact ventricular septum (PA-IVS) is a rare congenital cardiac disease characterized by atresia of the pulmonary valve, resulting in the absence of a connection between the right ventricular outflow tract and pulmonary arteries. PA-IVS is characterized by varying degrees of right ventricular hypoplasia: from single ventricle palliation (1v) to 1½-ventricle palliation (1.5v) and bi-ventricle repair (2v). To understand how cardiac development is impaired in PA-IVS-1v, we generated PA-IVS-1v patient-specific induced pluripotent stem cells (iPSCs). We then ran single-cell RNA-seq to temporally profile transcriptomic changes during cardiac differentiation in healthy control (Control) and PA-IVS-1v iPSCs. We collected differentiating cells at multiple time points corresponding to different development stages, ie. Day 5 (cardiac mesoderm), Day 10 (cardiac progenitor), Day 14 (early cardiomyocyte), and Day 30 (fetal cardiomyocyte). Single-cell transcriptomic analysis indicates that cell lineage commitment of cardiac progenitors is skewed towards epicardial and first heart field progenitors in the differentiating iPSCs from PA-IVS-1v.