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Generation of Induced Pluripotent Stem Cells from Muscular Dystrophy Patients: Efficient Integration-free Reprogramming of Urine Derived Cells
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Dystrophic muscle environment induces changes in cell plasticity.

Herve Faralli1, F Jeffrey Dilworth

  • 1Sprott Center for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Ontario K1H 8L6, Canada;

Genes & Development
|April 17, 2014
PubMed
Summary

Muscle stem cells called fibro-adipogenic progenitors (FAPs) gain the ability to form muscle fibers in a dystrophic environment. Deacetylase inhibitors activate a specific gene network, promoting muscle regeneration by FAPs.

Keywords:
BAF60FAPsHDACSWI/SNF chromatin remodelingmicroRNAmuscular dystrophy

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Area of Science:

  • Muscle biology
  • Cellular differentiation
  • Regenerative medicine

Background:

  • Fibro-adipogenic progenitors (FAPs) are crucial for muscle repair but typically lack myogenic potential.
  • Under normal conditions, FAPs do not directly contribute to regenerated myofibers.

Purpose of the Study:

  • To investigate the plasticity of FAPs in a dystrophic muscle environment.
  • To identify mechanisms that can induce myogenic potential in FAPs.

Main Methods:

  • Analysis of FAP chromatin state in dystrophic muscle.
  • Treatment with deacetylase inhibitors.
  • Investigation of the BAF60c-myomiR transcriptional network.

Main Results:

  • The dystrophic muscle environment induces a myogenic-competent chromatin state in FAPs.
  • Deacetylase inhibitors activate a BAF60c-myomiR network in FAPs.
  • This activation blocks adipogenesis and promotes muscle differentiation.

Conclusions:

  • FAPs can acquire myogenic potential under specific pathological conditions.
  • Targeting epigenetic regulators like deacetylase inhibitors offers a therapeutic strategy to enhance muscle regeneration by FAPs.