title: Comparative gene expression profiling in human-induced pluripotent stem cell--derived cardiocytes and human and cynomolgus heart tissue.
abstract: Cardiotoxicity is one of the leading causes of drug attrition. Current in vitro models insufficiently predict cardiotoxicity, and there is a need for alternative physiologically relevant models. Here we describe the gene expression profile of human-induced pluripotent stem cell-derived cardiocytes (iCC) postthaw over a period of 42 days in culture and compare this profile to human fetal and adult as well as adult cynomolgus nonhuman primate (NHP, Macaca fascicularis) heart tissue. Our results indicate that iCC express relevant cardiac markers such as ion channels (SCN5A, KCNJ2, CACNA1C, KCNQ1, and KCNH2), tissue-specific structural markers (MYH6, MYLPF, MYBPC3, DES, TNNT2, and TNNI3), and transcription factors (NKX2.5, GATA4, and GATA6) and lack the expression of stem cell markers (FOXD3, GBX2, NANOG, POU5F1, SOX2, and ZFP42). Furthermore, we performed a functional evaluation of contractility of the iCC and showed functional and pharmacological correlations with myocytes isolated from adult NHP hearts. These results suggest that stem cell-derived cardiocytes may represent a novel in vitro model to study human cardiac toxicity with potential ex vivo and in vivo translation.
authors.affiliation: Compound Safety Prediction, Pfizer, Inc., Groton, Connecticut 06340, USA. Dinesh.Puppala@pfizer.com
authors.forename: Dinesh
authors.initials: D
authors.lastname: Puppala
authors.forename: Leon P
authors.initials: LP
authors.lastname: Collis
authors.forename: Sunny Z
authors.initials: SZ
authors.lastname: Sun
authors.forename: Vinicius
authors.initials: V
authors.lastname: Bonato
authors.forename: Xian
authors.initials: X
authors.lastname: Chen
authors.forename: Blake
authors.initials: B
authors.lastname: Anson
authors.forename: Mathew
authors.initials: M
authors.lastname: Pletcher
authors.forename: Bernard
authors.initials: B
authors.lastname: Fermini
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Engle
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D004353:Drug Evaluation, Preclinical; D064420:Drug-Related Side Effects and Adverse Reactions; D020869:Gene Expression Profiling; D006801:Humans; D008252:Macaca fascicularis; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology*; D059467:Transcriptome / Q000187:drug effects*