Core Transcription Factors Promote Induction of PAX3-Positive Skeletal Muscle Stem Cells

Stem Cell Reports. 2019 Aug 13;13(2):352-365. doi: 10.1016/j.stemcr.2019.06.006. Epub 2019 Jul 25.


The use of adult skeletal muscle stem cells (MuSCs) for cell therapy has been attempted for decades, but still encounters considerable difficulties. MuSCs derived from human induced pluripotent stem cells (hiPSCs) are promising candidates for stem cell therapy to treat Duchenne muscular dystrophy (DMD). Here we report that four transcription factors, HEYL, KLF4, MYOD, and PAX3, selected by comprehensive screening of different MuSC populations, enhance the derivation of PAX3-positive myogenic progenitors from fibroblasts and hiPSCs, using medium that promotes the formation of presomitic mesoderm. These induced PAX3-positive cells contribute efficiently to the repair of DMD-damaged myofibers and also reconstitute the MuSC population. These studies demonstrate how a combination of core transcription factors can fine-tune the derivation of MuSCs capable of contributing to the repair of adult skeletal muscle.

Keywords: Pax3; hiPSC; muscle stem cell; muscular dystrophy; reprogramming.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cell Differentiation
  • Disease Models, Animal
  • Dystrophin / deficiency
  • Dystrophin / genetics
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / metabolism
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism
  • Mesoderm / cytology
  • Mesoderm / metabolism
  • Mice
  • Mice, Inbred NOD
  • Mice, Knockout
  • Muscle Development
  • Muscle, Skeletal / cytology*
  • Muscle, Skeletal / metabolism
  • Muscular Dystrophy, Duchenne / therapy
  • MyoD Protein / genetics
  • MyoD Protein / metabolism
  • PAX3 Transcription Factor / genetics
  • PAX3 Transcription Factor / metabolism*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Stem Cell Transplantation
  • Stem Cells / cytology
  • Stem Cells / metabolism


  • Basic Helix-Loop-Helix Transcription Factors
  • Dystrophin
  • GKLF protein
  • HEYL protein, human
  • Kruppel-Like Transcription Factors
  • MyoD Protein
  • PAX3 Transcription Factor
  • Repressor Proteins