ERBB3 and NGFR mark a distinct skeletal muscle progenitor cell in human development and hPSCs

Nat Cell Biol. 2018 Jan;20(1):46-57. doi: 10.1038/s41556-017-0010-2. Epub 2017 Dec 18.


Human pluripotent stem cells (hPSCs) can be directed to differentiate into skeletal muscle progenitor cells (SMPCs). However, the myogenicity of hPSC-SMPCs relative to human fetal or adult satellite cells remains unclear. We observed that hPSC-SMPCs derived by directed differentiation are less functional in vitro and in vivo compared to human satellite cells. Using RNA sequencing, we found that the cell surface receptors ERBB3 and NGFR demarcate myogenic populations, including PAX7 progenitors in human fetal development and hPSC-SMPCs. We demonstrated that hPSC skeletal muscle is immature, but inhibition of transforming growth factor-β signalling during differentiation improved fusion efficiency, ultrastructural organization and the expression of adult myosins. This enrichment and maturation strategy restored dystrophin in hundreds of dystrophin-deficient myofibres after engraftment of CRISPR-Cas9-corrected Duchenne muscular dystrophy human induced pluripotent stem cell-SMPCs. The work provides an in-depth characterization of human myogenesis, and identifies candidates that improve the in vivo myogenic potential of hPSC-SMPCs to levels that are equal to directly isolated human fetal muscle cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • CRISPR-Cas Systems
  • Cell Differentiation
  • Dystrophin / genetics
  • Dystrophin / metabolism
  • Female
  • Gene Editing
  • Gene Expression Regulation, Developmental
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / metabolism
  • Male
  • Middle Aged
  • Muscle Development / genetics*
  • Muscle Fibers, Skeletal / cytology
  • Muscle Fibers, Skeletal / metabolism*
  • Muscular Dystrophy, Duchenne / genetics*
  • Muscular Dystrophy, Duchenne / metabolism
  • Muscular Dystrophy, Duchenne / pathology
  • Muscular Dystrophy, Duchenne / therapy
  • Myoblasts / cytology
  • Myoblasts / metabolism*
  • Myosins / genetics
  • Myosins / metabolism
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • PAX7 Transcription Factor / genetics
  • PAX7 Transcription Factor / metabolism
  • Receptor, ErbB-3 / genetics*
  • Receptor, ErbB-3 / metabolism
  • Receptors, Nerve Growth Factor / genetics*
  • Receptors, Nerve Growth Factor / metabolism
  • Signal Transduction
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism


  • Dystrophin
  • NGFR protein, human
  • Nerve Tissue Proteins
  • PAX7 Transcription Factor
  • PAX7 protein, human
  • Receptors, Nerve Growth Factor
  • Transforming Growth Factor beta
  • ERBB3 protein, human
  • Receptor, ErbB-3
  • Myosins