Probing single ventricle heart defects with patient-derived induced pluripotent stem cells and emerging technologies.

Abstract

Single ventricle heart defects (SVHDs) are a severe type of congenital heart disease with poorly understood pathogenic mechanisms. New research using patient-specific induced pluripotent stem cells (iPSCs) as a cellular model is beginning to uncover genetic and cellular etiologies of SVHDs. Hypoplastic left heart syndrome (HLHS) is a type of SVHD that is characterized by an underdeveloped left ventricle and other malformations in the left side of the heart. Hypoplastic right heart syndrome (HRHS), the second type of SVHD, is characterized by an underdeveloped right heart, including malformed tricuspid and pulmonary valves. Despite a noticeable lack of research on SVHD, emerging technologies offer a promising future to further probe the genetic and cellular mechanisms of these diseases. Pediatric cardiovascular research is at the dawn of a new era in terms of what can be discovered with patient-specific iPSCs in conjunction with other technologies (e.g., organoids, single-cell genomics, CRISPR/Cas9 genome editing). In this review, we present recent approaches and findings utilizing patient-specific iPSCs to identify cellular mechanisms responsible for improper cardiac organogenesis in HLHS and HRHS.