Kavitha S. Rao1,2,4, Vasumathi Kameswaran1,2,4 and Benoit G. Bruneau1,2,3 1Gladstone Institutes, San Francisco, California 94158, USA; 2Roddenberry Center for Stem Cell Biology and Medicine at Gladstone, San Francisco, California 94158, USA; 3Department of Pediatrics and Cardiovascular Research Institute, University of California at San Francisco, San Francisco, California 94158, USA Corresponding author: benoit.bruneaugladstone.ucsf.edu

↵4 These authors contributed equally to this work.

Abstract

Congenital heart defects (CHDs) are among the most common birth defects, but their etiology has long been mysterious. In recent decades, the development of a variety of experimental models has led to a greater understanding of the molecular basis of CHDs. In this review, we contrast mouse models of CHD, which maintain the anatomical arrangement of the heart, and human cellular models of CHD, which are more likely to capture human-specific biology but lack anatomical structure. We also discuss the recent development of cardiac organoids, which are a promising step toward more anatomically informative human models of CHD.