TITLE

Direct differentiation of atrial and ventricular myocytes from human embryonic stem cells by alternating retinoid signals

AUTHOR(S)
Zhang, Qiangzhe; Jiang, Junjie; Han, Pengcheng; Yuan, Qi; Zhang, Jing; Zhang, Xiaoqian; Xu, Yanyan; Cao, Henghua; Meng, Qingzhang; Chen, Li; Tian, Tian; Wang, Xin; Li, Pu; Hescheler, Jurgen; Ji, Guangju; Ma, Yue
PUB. DATE
April 2011
SOURCE
Cell Research;Apr2011, Vol. 21 Issue 4, p579
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
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 pan-retinoic 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.
ACCESSION #
59816487

 

Related Articles

  • Three-Ingredient Cocktail Makes Heart Cells from Stem Cells. Breindl, Anette // BioWorld Today;5/6/2009, Vol. 20 Issue 86, p1 

    The article discusses research being done on the use of stem cells to develop heart cells. It references a study by Benoit Bruneau and colleagues, published in the April 26, 2009 online issue of "Nature." The study defined the three factors that are considered necessary to turn embryonic stem...

  • Shortcuts to making cardiomyocytes. Huansheng Xu; Yi, B. Alexander; Chien, Kenneth R. // Nature Cell Biology;Mar2011, Vol. 13 Issue 3, p191 

    The adult human heart lacks sufficient regenerative capacity to recover after a myocardial infarction. Cell-based therapy has emerged as a potential treatment for the failing heart; however, a key issue for the success of future cell-based therapies is the ability to obtain patient-specific...

  • Forever Young. Richardson, Sarah // Discover;Jan99, Vol. 20 Issue 1, p58 

    Reports on the successful isolation of human embryonic stem cells by two laboratories in 1998. Importance of the development to efforts to grow customized tissues; Growth of cells under various conditions; Questions on ethics raised by stem cell research.

  • Poster session 2.  // Cardiovascular Research;Mar2012 Supplement 1, Vol. 93 Issue suppl_1, pS52 

    No abstract available.

  • Excitation spread between heart cells derived from embryonic stem (ES) cells.  // Pflugers Archiv European Journal of Physiology;Apr2000 Supplement, Vol. 439, pR368 

    An abstract of the study "Excitation spread between heart cells derived from embryonic stem (ES) cells" is presented. It examines the spread of excitation in spontaneously formed tissue clusters using an in vitro system for differentiating ES cells into cardiac myocytes. It also determines the...

  • Highly efficient derivation of ventricular cardiomyocytes from induced pluripotent stem cells with a distinct epigenetic signature. Xu, Huansheng; Yi, B Alexander; Wu, Hao; Bock, Christoph; Gu, Hongcang; Lui, Kathy O; Park, Joo-Hye C; Shao, Ying; Riley, Alyssa K; Domian, Ibrahim J; Hu, Erding; Willette, Robert; Lepore, John; Meissner, Alexander; Wang, Zhong; Chien, Kenneth R // Cell Research;Jan2012, Vol. 22 Issue 1, p142 

    Cardiomyocytes derived from pluripotent stem cells can be applied in drug testing, disease modeling and cell-based therapy. However, without procardiogenic growth factors, the efficiency of cardiomyogenesis from pluripotent stem cells is usually low and the resulting cardiomyocyte population is...

  • Regulation of Ca2+ signaling during differentiation of embryonic stem cells into cardiomyocytes and neuronal cells. Huantian Yang; Huimei Yu; Ji-Dong Fu; Jun Li; Rong Wang; Ji Liang; Ang Guo; Jing Wen; Wan-Hua Shen; Shumin Duan; Boheler, Kenneth R. // Cell Research;Aug2008 Supplement, Vol. 18, pS102 

    Proper intracellular Ca[sup2+] signaling is essential for cell functions. However, the significance of intracellular calcium concentration ([Ca[sup2+]][subi]) regulated by Ca[sup2+] release from endoplasmic reticulum (ER) during early developmental stage of myocytes and neuronal cells have not...

  • High efficient differentiation of (embryonic) stem cells into cardiac myocytes: introduction of a new inducer. Lin Miao; Min Wang; Wenxuan Yin; Guangju Ji // Cell Research;Aug2008 Supplement, Vol. 18, pS60 

    Stem cell-derived cardiac myocytes have been transplanted in experimental settings to replace lost myocardial tissue, and this has been shown to improve myocardial function in animal experiments. Stem cell-derived cardiomyocytes in particular, either of embryonic or bone marrow cell origin, will...

  • Large Stem Cell-Derived Cardiomyocyte Grafts: Cellular Ventricular Assist Devices? Harding, Sian E // Molecular Therapy;Jul2014, Vol. 22 Issue 7, p1240 

    The article presents the author's views on large stem cell-derived cardiomyocyte grafts. It discusses research studies related to the use of cellular ventricular assist devices. It is stated that the human embryonic stem cells (hESCs) or human induced pluripotent stem cells (hiPSCs) can reliably...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics