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Direct differentiation of atrial and ventricular myocytes from human embryonic stem cells by alternating retinoid signals
文献类型：期刊论文
| 作者 | Zhang, QZ; Jiang, JJ; Han, PC; Yuan, Q; Zhang, J; Zhang, XQ; Xu, YY; Cao, HH; Meng, QZ; Chen, L |
| 刊名 | CELL RESEARCH
 |
| 出版日期 | 2011 |
| 卷号 | 21期号:4页码:579-587 |
| 关键词 | human embryonic stem cell cardiac subtype specification heart development |
| 通讯作者 | Ma, Y (reprint author), Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, 15 Datun Rd, Beijing 100101, Peoples R China.,gj28@ibp.ac.cn ; yuema@ibp.ac.cn |
| 英文摘要 | Although myocyte cell transplantation studies have suggested a promising therapeutic potential for myocardial infarction, a major obstacle to the development of clinical therapies for myocardial repair is the difficulties associated with obtaining relatively homogeneous ventricular myocytes for transplantation. Human embryonic stem cells (hESCs) are a promising source of cardiomyocytes. Here we report that retinoid signaling regulates the fate specification of atrial versus ventricular myocytes during cardiac differentiation of hESCs. We found that both Noggin and the panretinoic acid receptor antagonist BMS-189453 (RAi) significantly increased the cardiac differentiation efficiency of hESCs. To investigate retinoid functions, we compared Noggin+RAi-treated cultures with Noggin+RA-treated cultures. Our results showed that the expression levels of the ventricular-specific gene IRX-4 were radically elevated in Noggin+RAi-treated cultures. MLC-2V, another ventricular-specific marker, was expressed in the majority of the cardiomyocytes in Noggin+RAi-treated cultures, but not in the cardiomyocytes of Noggin+RA-treated cultures. Flow cytometry analysis and electrophysiological studies indicated that with 64.7 +/- 0.88% (mean +/- s.e.m) cardiac differentiation efficiency, 83% of the cardiomyocytes in Noggin+RAi-treated cultures had embryonic ventricular-like action potentials (APs). With 50.7 +/- 1.76% cardiac differentiation efficiency, 94% of the cardiomyocytes in Noggin+RA-treated cultures had embryonic atrial-like APs. These results were further confirmed by imaging studies that assessed the patterns and properties of the Ca2+ sparks of the cardiomyocytes from the two cultures. These findings demonstrate that retinoid signaling specifies the atrial versus ventricular differentiation of hESCs. This study also shows that relatively homogeneous embryonic atrial-and ventricular-like myocyte populations can be efficiently derived from hESCs by specifically regulating Noggin and retinoid signals. |
| 学科主题 | Cell Biology |
| 类目[WOS] | Cell Biology |
| 关键词[WOS] | FOCAL CA2+ RELEASE ; CARDIAC MYOCYTES ; PROGENITOR CELLS ; IN-VITRO ; CARDIOMYOCYTES ; HEART ; INHIBITION ; INDUCTION ; MESODERM ; PROLIFERATION |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000289230800005 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/777]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Zhang, QZ,Jiang, JJ,Han, PC,et al. Direct differentiation of atrial and ventricular myocytes from human embryonic stem cells by alternating retinoid signals[J]. CELL RESEARCH,2011,21(4):579-587. |
| APA | Zhang, QZ.,Jiang, JJ.,Han, PC.,Yuan, Q.,Zhang, J.,...&Ma, Y.(2011).Direct differentiation of atrial and ventricular myocytes from human embryonic stem cells by alternating retinoid signals.CELL RESEARCH,21(4),579-587. |
| MLA | Zhang, QZ,et al."Direct differentiation of atrial and ventricular myocytes from human embryonic stem cells by alternating retinoid signals".CELL RESEARCH 21.4(2011):579-587. |
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