Abstract: Human pluripotent stem cells (hPSCs) can be directed to differentiate into skeletal muscle progenitor cells (SMPCs). However, the myogenic potential of hPSC-SMPCs compared to human fetal or adult satellite cells (Scs) remains unclear.  This study demonstrates hPSC-SMPCs derived by commonly used protocols are functionally less mature than freshly-isolated human fetal or adult Scs.  We utilized RNA-SEQ of human fetal Scs to identify differentially expressed genes including NGFR, ERBB3, which enriched for MYOD+ or PAX7+ cells.  Furthermore, inhibition of TGF (TGFi) improved hPSC-muscle maturation in three independent lines as measured by TEM and expression of myosins. Engraftment of CRISPR/Cas9-corrected Duchenne Muscular Dystrophy (DMD) hiPSC-SMPC subpopulations treated with TGFi in vivo, increased dystrophin-positive fibers to levels of engrafted cultured fetal Scs in mdx mouse models of DMD.  This work provides the first characterization of the developmental status of hPSC-SMPCs and identifies candidates to enable robust myogenic activity in vitroandin vivo. SOURCE: Ascia EskinStanley Nelson UCLA

Pluto Bioinformatics

GSE87365: ERBB3 and NGFR mark distinct skeletal muscle progenitor cells in human development enabling enrichment and maturation of hPSC muscle