Human Pluripotent Stem Cell-Derived Atrial and Ventricular Cardiomyocytes Develop from Distinct Mesoderm Populations

Publication date: 3 August 2017
Source:Cell Stem Cell, Volume 21, Issue 2
Author(s): Jee Hoon Lee, Stephanie I. Protze, Zachary Laksman, Peter H. Backx, Gordon M. Keller
The ability to direct the differentiation of human pluripotent stem cells (hPSCs) to the different cardiomyocyte subtypes is a prerequisite for modeling specific forms of cardiovascular disease in vitro and for developing novel therapies to treat them. Here we have investigated the development of the human atrial and ventricular lineages from hPSCs, and we show that retinoic acid signaling at the mesoderm stage of development is required for atrial specification. Analyses of early developmental stages revealed that ventricular and atrial cardiomyocytes derive from different mesoderm populations that can be distinguished based on CD235a and RALDH2 expression, respectively. Molecular and electrophysiological characterization of the derivative cardiomyocytes revealed that optimal specification of ventricular and atrial cells is dependent on induction of the appropriate mesoderm. Together these findings provide new insights into the development of the human atrial and ventricular lineages that enable the generation of highly enriched, functional cardiomyocyte populations for therapeutic applications.

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Keller, Protze, and colleagues show that atrial and ventricular cardiomyocytes develop from distinct mesoderm populations. Molecular and functional analyses revealed that appropriate mesoderm patterning is required for generating enriched populations of atrial or ventricular cardiomyocytes from hPSCs. These findings provide important new insights for the derivation of populations for future therapeutic applications.


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