Why the study?
Pluripotent stem cell-derived cardiomyocytes exhibit immature phenotypes limiting their applications, and current physical and functional maturation analyses are time-consuming and challenging.
A novel Myom2-RFP fluorescent reporter system enables rapid assessment of cardiomyocyte maturation and identified laminin-511/521 as potent maturation enhancers.
May streamline PSC-CM maturity assessment in vitro; leaves open clinical translation for disease modeling.
Pluripotent stem cell-derived cardiomyocytes (PSC-CMs) hold great promise for disease modeling and drug discovery. However, PSC-CMs exhibit immature phenotypes in culture, and the lack of maturity limits their broad applications. While physical and functional analyses are generally used to determine the status of cardiomyocyte maturation, they could be time-consuming and often present challenges in comparing maturation-enhancing strategies. Therefore, there is a demand for a method to assess cardiomyocyte maturation rapidly and reproducibly. In this study, we found that Myomesin-2 ( Myom2 ), encoding M-protein, is upregulated postnatally, and based on this, we targeted TagRFP to the Myom2 locus in mouse embryonic stem cells. Myom2-RFP + PSC-CMs exhibited more mature phenotypes than RFP - cells in morphology, function and transcriptionally, conductive to sarcomere shortening assays. Using this system, we screened extracellular matrices (ECMs) and identified laminin-511/521 as potent enhancers of cardiomyocyte maturation. Together, we developed and characterized a novel fluorescent reporter system for the assessment of cardiomyocyte maturation and identified potent maturation-enhancing ECMs through this simple and rapid assay. This system is expected to facilitate use of PSC-CMs in a variety of scientific and medical investigations.
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Chanthra et al. (2020) studied this question.
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