A human pluripotent stem cell model of facioscapulohumeral muscular dystrophy-affected skeletal muscles

Leslie Caron, Devaki Kher, Kian Leong Lee, Robert McKernan, Biljana Dumevska, Alejandro Hidalgo, Jia Li, Henry Yang, Heather Main, Giulia Ferri, Lisa M. Petek, Lorenz Poellinger, Daniel G. Miller, Davide Gabellini, Uli Schmidt

Research output: Contribution to journalArticlepeer-review


Facioscapulohumeral muscular dystrophy (FSHD) represents a major unmet clinical need arising from the progressive weakness and atrophy of skeletal muscles. The dearth of adequate experimental models has severely hampered our understanding of the disease. To date, no treatment is available for FSHD. Human embryonic stem cells (hESCs) potentially represent a renewable source of skeletal muscle cells (SkMCs) and provide an alternative to invasive patient biopsies. We developed a scalable monolayer system to differentiate hESCs into mature SkMCs within 26 days, without cell sorting or genetic manipulation. Here we show that SkMCs derived from FSHD1-affected hESC lines exclusively express the FSHD pathogenic marker double homeobox 4 and exhibit some of the defects reported in FSHD. FSHD1 myotubes are thinner when compared with unaffected and Becker muscular dystrophy myotubes, and differentially regulate genes involved in cell cycle control, oxidative stress response, and cell adhesion. This cellular model will be a powerful tool for studying FSHD and will ultimately assist in the development of effective treatments for muscular dystrophies.

Original languageEnglish
Pages (from-to)1145-1161
Number of pages17
JournalStem cells translational medicine
Issue number9
Publication statusPublished - 2016


  • Embryonic stem cells
  • Induced pluripotent stem cells
  • Muscular dystrophy
  • Pluripotent stem cells
  • Skeletal muscle

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology


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