HESC‐Derived Definitive Endoderm Induces Cardiomyogenesis in Human Embryonic Stem Cells.

Abstract

This laboratory previously reported that chick anterolateral endoderm (AL endoderm) potently induces cardiac myogenesis in mouse embryoid bodies. The requirement to microdissect AL endoderm from gastrulation‐stage embryos precludes the utilization of this tissue to identify cardiomyogenic factors. To overcome these limitations we have assessed whether human definitive endoderm (hDE) cells can mimic AL endoderm. Results indicate that while hDE does not share the cardiomyogenic potency of AL endoderm, both hDE cells and medium conditioned by them significantly enrich cardiac myogenesis in pluripotent hESCs as indicated by rhythmic beating and immunohistochemical/qPCR monitoring of marker gene expression. This response appears to be cardiomyocyte‐specific, since endothelial cell markers are unaffected. The cardiomyogenic effect of hDE is further enhanced when pluripotent hESCs are pre‐induced to mes‐endoderm. These findings demonstrate that, like chick AL endoderm, hDE induces cardiomyogenesis in pluripotent cells, and even more effectively in cells at early stages of mesoderm differentiation (mes‐endoderm). Because this approach is tractable and scalable it should facilitate the identification of novel hDE‐secreted factors, for inclusion in defined cardiomyogenic cocktails to generate homogeneous populations of human cardiomyocytes for use in experimental cell therapy.Grant Funding Source: NIH