Induced Pluripotent Stem Cells in Patients with Congenital Heart Disease

The recently developed technology of induced pluripotent stem cells (iPSCs) and defined protocols for directed cardiomyocyte differentiation allow the investigation of diseases using patient-specific cells in vitro for the first time.

In order to study the underlying etiology of Tetralogy of Fallot (TOF), a severe heart malformation, the establishment of patient-specific iPSCs and their differentiation into cardiomyocytes is assumed to be a valuable model.

Patient-specific iPSCs of two well-characterized TOF patients, harboring deleterious rare and/or private mutations, have been generated in addition to the generation of iPSCs from healthy relatives which serve as controls. Aiming to investigate the disease-specific phenotype in vitro, a comparative analysis of the differentiation and proliferation potential during cardiac differentiation will be performed. The analysis of the transcriptome aims to unravel the deregulated transcriptional network that underlies TOF and the influence of detected mutations on the expression of important cardiac modulators.

The combination of gene expression profiles and genome-wide data on chromatin structure is assumed to result, beyond disease-causing mutations in target genes, in an epigenetic explanation of the pathogenesis of TOF possibly linking genomic mutations in the affected individuals to the environmental impact.