Independent compartmentalization of functional, metabolic, and transcriptional maturation of hiPSC-derived cardiomyocytes
K. Ashley Fetterman,
Malorie Blancard,
Davi M. Lyra-Leite,
Carlos G. Vanoye,
Hananeh Fonoudi,
Mariam Jouni,
Jean-Marc L. DeKeyser,
Brian Lenny,
Yadav Sapkota,
Alfred L. George, Jr.,
Paul W. Burridge
Affiliations
K. Ashley Fetterman
Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Center for Pharmacogenomics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
Malorie Blancard
Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Center for Pharmacogenomics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
Davi M. Lyra-Leite
Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Center for Pharmacogenomics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
Carlos G. Vanoye
Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
Hananeh Fonoudi
Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Center for Pharmacogenomics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
Mariam Jouni
Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Center for Pharmacogenomics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
Jean-Marc L. DeKeyser
Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Center for Pharmacogenomics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
Brian Lenny
Department of Epidemiology and Cancer Control, St. Jude Children’s Hospital, Memphis, TN, USA
Yadav Sapkota
Department of Epidemiology and Cancer Control, St. Jude Children’s Hospital, Memphis, TN, USA
Alfred L. George, Jr.
Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Center for Pharmacogenomics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
Paul W. Burridge
Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Center for Pharmacogenomics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Corresponding author
Summary: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) recapitulate numerous disease and drug response phenotypes, but cell immaturity may limit their accuracy and fidelity as a model system. Cell culture medium modification is a common method for enhancing maturation, yet prior studies have used complex media with little understanding of individual component contribution, which may compromise long-term hiPSC-CM viability. Here, we developed high-throughput methods to measure hiPSC-CM maturation, determined factors that enhanced viability, and then systematically assessed the contribution of individual maturation medium components. We developed a medium that is compatible with extended culture. We discovered that hiPSC-CM maturation can be sub-specified into electrophysiological/EC coupling, metabolism, and gene expression and that induction of these attributes is largely independent. In this work, we establish a defined baseline for future studies of cardiomyocyte maturation. Furthermore, we provide a selection of medium formulae, optimized for distinct applications and priorities, that promote measurable attributes of maturation.