17Comparative genomic studies in primates have the potential to reveal the genetic and 18 mechanistic basis for human specific traits. These studies may also help us better understand 19inter-species phenotypic differences that are clinically relevant. Unfortunately, the obvious 20 limitation on sample collection and experimentation in humans and non-human apes severely 21 restrict our ability to perform dynamic comparative studies in primates. Induced pluripotent 22 stem cells (iPSCs), and their corresponding differentiated cells, may provide a suitable 23 alternative system for dynamic comparative studies. Yet, to effectively use iPSCs and 24 differentiated cells for comparative studies, one must characterize the extent to which these 25 systems faithfully represent biological processes in primary tissues. To do so, we compared 26 gene expression data from primary adult heart tissue and iPSC-derived cardiomyocytes from 27 multiple human and chimpanzee individuals. We determined that gene expression in cultured 28 cardiomyocytes from both human and chimpanzee is most similar to that of adult hearts 29 compared to other adult tissues. Using a comparative framework, we found that 50% of gene 30 regulatory differences between human and chimpanzee hearts are also observed between 31 species in cultured cardiomyocytes; conversely, inter-species regulatory differences seen in 32 cardiomyocytes are found significantly more often in hearts than in other primary tissues. Our 33 work provides a detailed description of the utility and limitation of differentiated 34 cardiomyocytes as a system for comparative functional genomic studies in primates. 35 36 Data availability and resource sharing 37 Gene expression (RNA-seq) data are available at GEO under accession number GSE110471. All 38 human and chimpanzee iPSCs are available upon request without restriction or limitation. 39 40 41 42 43