EMBRYONIC STEM CELLS/INDUCED PLURIPOTENT STEM CELLS Embryonic Stem Cell-Derived Cardiomyogenesis: A Novel Role for

A role for calreticulin, an endoplasmic reticulum (ER)-resi-dent, Ca21-binding chaperone, has recently emerged in the context of cardiomyogenesis. We previously proposed calre-ticulin to be a novel cardiac fetal gene, because calreticulin knockout causes embryonic lethality in mice as a result of cardiac defects, it is transiently activated during heart development, and heart-targeted overexpression of constitu-tively active calcineurin in calreticulin-null mice rescues the lethal phenotype. Calreticulin affects Ca21 homeostasis and expression of adhesion-related genes. Using cardiomyocytes derived from both calreticulin-null and wild-type embry-onic stem (ES) cells, we show here that cardiomyogenesis from calreticulin-null ES cells is accelerated but deregu-lated, such that the myofibrils of calreticulin-null cardiomy