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Neuregulin-1 promotes cardiomyocyte differentiation of genetically engineered embryonic stem cell clones

  • Wang, Zhi (Department of Cardiology, The First People’s Hospital, Shanghai Jiaotong University School of Medicine) ;
  • Xu, Guotong (Key Laboratory of Stem Cell Biology, Institute of Health Sciences and Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Science, Chinese Academy of Science) ;
  • Wu, Yalan (Key Laboratory of Stem Cell Biology, Institute of Health Sciences and Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Science, Chinese Academy of Science) ;
  • Liu, Shaowen (Department of Cardiology, The First People’s Hospital, Shanghai Jiaotong University School of Medicine) ;
  • Sun, Baogui (Department of Cardiology, The First People’s Hospital, Shanghai Jiaotong University School of Medicine) ;
  • Dai, Qiuyan (Department of Cardiology, The First People’s Hospital, Shanghai Jiaotong University School of Medicine)
  • Published : 2008.10.31

Abstract

Embryonic stem (ES) cell-derived cardiomyocytes (ESCMs) must be specifically purified in order to prevent teratoma formation, and this confusing issue has hampered their clinical application. We therefore investigated a technique to generate pure labeled ESCMs for possible use in cardiac repair. We generated transgenic ES cell lines expressing enhanced green fluorescent protein (EGFP) under the transcriptional control of the $\alpha$-cardiac myosin heavy chain ($\alpha$-MHC) promoter. Differentiated EGFP-positive ES cells displayed characteristics of CMs. Furthermore, neuregulin-1 (NRG-1) upregulated the expression of the cardiac-restricted transcription factors Nkx2.5 and GATA-4, as well as differentiated CM factors ($\alpha$-MHC, $\beta$-MHC). Immunohistochemistry demonstrated that NRG-1 increased expression of cardiac-specific troponin T in the beating foci of the embryoid bodies. This work revealed a potential method for specifically labeling and enriching ESCMs by combining genetically-engineered ES cell clones and exogenous growth factor treatment.

Keywords

References

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