Expression profiles of histone lyslne demethylases during cardiomyocyte differentiation of mouse embryonic stem cells

Aim： Histone lysine demethylases （KDMs） control the lineage commitments of stem cells. However, the KDMs involved in the determination of the cardiomyogenic lineage are not fully defined. The aim of this study was to investigate the expression profiles of KDMs during the cardiac differentiation of mouse embryonic stem cells （mESCs）. Methods： An in vitro cardiac differentiation system of mESCs with Brachyury （a mesodermal specific marker） and FIk-1^＋/Cxcr4^＋ （dual cell surface biomarkers） selection was used. The expression profiles of KDMs during differentiation were analyzed using Q-PCR. To understand the contributions of KDMs to cardiomyogenesis, the mESCs on differentiation d 3.5 were sorted by FACS into Brachyury^＋ cells and Brachyury cells, and mESCs on d 5.5 were sorted into FIk-1^＋/Cxcr4^＋ and FIk-1-/Cxcr4- cells. Results： mESCs were differentiated into spontaneously beating cardiomyocytes that were visible in embryoid bodies （EBs） on d 7. On d 12-14, all EBs developed spontaneously beating cardiomyocytes. Among the 16 KDMs examined, the expression levels of Phf8, Jaridla, Jhdmld, Utx, and Jmjd3 were increased by nearly 2-6-fold on d 14 compared with those on d O. Brachyury^＋ cells showed higher expression levels of Jmjd3, Jmjd2a and Jhdmld than Brachyury- cells. A higher level of Jmjd3 was detected in FIk-1^＋/Cxcr4^＋ cells, whereas the level of Jmjd2c was lower in both Brachyury^＋ cells and FIk-1^＋/Cxcr4^＋ cells. Conclusion： KDMs may play important roles during cardiomyogenesis of mESCs. Our results provide a clue for further exploring the roles of KDMs in the cardiac lineage commitment of mESCs and the potential interference of cardiomyogenesis.