@article{APS7965,
author = {Yan TANG and Zhong-yan CHEN and Ya-zhen HONG and Qiang WU and Han-qing LIN and Charlie Degui CHEN and Huang-tian YANG},
title = {Expression profiles of histone lysine demethylases during cardiomyocyte differentiation of mouse embryonic stem cells},
journal = {Acta Pharmacologica Sinica},
volume = {35},
number = {7},
year = {2016},
keywords = {},
abstract = {Yan TANG1, Zhong-yan CHEN1, Ya-zhen HONG1, Qiang WU2, Han-qing LIN2, Charlie Degui CHEN2, Huang-tian YANG1, 3, *
1Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine/Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai 200031, China; 2State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, Institute of Biochemistry and Cell Biology, SIBS, CAS, Shanghai 200031, China; 3Second Affiliated Hospital, Zhejiang University, Hangzhou 310009, China
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 Flk-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 Flk-1+/Cxcr4+ and Flk-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, Jarid1a, Jhdm1d, Utx, and Jmjd3 were increased by nearly 2–6-fold on d 14 compared with those on d 0. Brachyury+ cells showed higher expression levels of Jmjd3, Jmjd2a and Jhdm1d than Brachyury– cells. A higher level of Jmjd3 was detected in Flk-1+/Cxcr4+ cells, whereas the level of Jmjd2c was lower in both Brachyury+ cells and Flk-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.
Keywords: embryonic stem cell; cardiac differentiation; cardiomyocyte; histone lysine demethylase; expression profile; Brachyury; Flk-1+/Cxcr4+
This study was supported by grants from the Strategic Priority Research Program of CAS (XDA01020204), the National Basic Research Program of China (2011CB965300 and 2014CB965100), and the National Natural Science Foundation of China (31030050). We thank Dr Gordon KELLER for kindly providing the Brachyury-GFP E14 mESCs.
* To whom correspondence should be addressed.
E-mail htyang@sibs.ac.cn
Received 2014-03-30 Accepted 2014-04-27},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/7965}
}