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Stem Cell Reviews and Reports

, Volume 8, Issue 2, pp 482–493 | Cite as

Retinoic Acid Enhances Skeletal Myogenesis in Human Embryonic Stem Cells by Expanding the Premyogenic Progenitor Population

  • Tammy Ryan
  • Jun Liu
  • Alphonse Chu
  • Lisheng Wang
  • Alexandre Blais
  • Ilona S. Skerjanc
Article

Abstract

Human embryonic stem cells (hESCs) are a potential source of material for cell therapy of muscle diseases. To date, it has proven difficult to generate skeletal muscle from hESCs in high yields and within a reasonable timeframe. Further, a hESC-derived Pax3/7-positive skeletal muscle progenitor population has not yet been described. Previous studies have shown that Pax3/7-positive progenitor cells can repopulate the satellite cell niche, indicating the importance of this population for therapy. We sought to optimize the differentiation of hESCs into skeletal muscle in order to characterize myogenesis at a molecular level and shorten the time course. We treated hESCs with retinoic acid (RA) and found an enhancement of skeletal myogenesis, and the expression of the myogenic regulatory factors (MRFs) MyoD and myogenin by day 25. Furthermore, we found that RA treatment expanded the muscle progenitor pool, which occurred as a distinct Pax3+ve population prior to MRF expression. Non-skeletal muscle tissue types were not significantly affected. Therefore, we have identified a differentiation pathway in hESCs that provides a skeletal muscle progenitor population which can undergo myogenesis more efficiently. We propose that RA could fit into a directed culture method for deriving skeletal muscle from hESCs.

Keywords

Embryonic stem cells Retinoic acid Myogenesis Cell differentiation 

Abbreviations

(hESCs)

human embryonic stem cells

(mESCs)

mouse embryonic stem cells

(EC) cells

P19 embryonal carcinoma

(RA)

retinoic acid

(iPS) cells

induced pluripotent stem

(MyHC)

myosin heavy hhain

Notes

Acknowledgements

We thank Anastassia Voronova for helpful comments and reading the manuscript. T.R. was supported by an OGSST award. This work was supported by a grant to I.S.S. from the Muscular Dystrophy Association (113716).

Conflicts of interest

The authors declare no potential conflicts of interest.

Supplementary material

12015_2011_9284_MOESM1_ESM.doc (44 kb)
Table 1 QPCR Primer sequences (DOC 43 kb)

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Tammy Ryan
    • 1
  • Jun Liu
    • 1
  • Alphonse Chu
    • 1
    • 2
  • Lisheng Wang
    • 1
  • Alexandre Blais
    • 1
    • 2
  • Ilona S. Skerjanc
    • 1
  1. 1.Department of Biochemistry, Microbiology and Immunology, Faculty of MedicineUniversity of OttawaOttawaCanada
  2. 2.Ottawa Institute of Systems BiologyOttawaCanada

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