Interleukin 4 Moderately Affects Competence of Pluripotent Stem Cells for Myogenic Conversion

Int J Mol Sci. 2019 Aug 13;20(16):3932. doi: 10.3390/ijms20163932.

Abstract

Pluripotent stem cells convert into skeletal muscle tissue during teratoma formation or chimeric animal development. Thus, they are characterized by naive myogenic potential. Numerous attempts have been made to develop protocols enabling efficient and safe conversion of pluripotent stem cells into functional myogenic cells in vitro. Despite significant progress in the field, generation of myogenic cells from pluripotent stem cells is still challenging-i.e., currently available methods require genetic modifications, animal-derived reagents, or are long lasting-and, therefore, should be further improved. In the current study, we investigated the influence of interleukin 4, a factor regulating inter alia migration and fusion of myogenic cells and necessary for proper skeletal muscle development and maintenance, on pluripotent stem cells. We assessed the impact of interleukin 4 on proliferation, selected gene expression, and ability to fuse in case of both undifferentiated and differentiating mouse embryonic stem cells. Our results revealed that interleukin 4 slightly improves fusion of pluripotent stem cells with myoblasts leading to the formation of hybrid myotubes. Moreover, it increases the level of early myogenic genes such as Mesogenin1, Pax3, and Pax7 in differentiating embryonic stem cells. Thus, interleukin 4 moderately enhances competence of mouse pluripotent stem cells for myogenic conversion.

Keywords: differentiation; embryonic stem cells; fusion; hybrid myotubes; interleukin 4; myogenesis; pluripotency.

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Line
  • Cell Self Renewal / genetics
  • Coculture Techniques
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / drug effects
  • Embryonic Stem Cells / metabolism
  • Gene Expression Regulation, Developmental
  • Interleukin-4 / genetics
  • Interleukin-4 / metabolism*
  • Interleukin-4 / pharmacology
  • Mice
  • Muscle Development
  • Muscle Fibers, Skeletal / cytology
  • Muscle Fibers, Skeletal / metabolism
  • Myoblasts / cytology
  • Myoblasts / drug effects
  • Myoblasts / metabolism
  • Pluripotent Stem Cells / cytology*
  • Pluripotent Stem Cells / drug effects
  • Pluripotent Stem Cells / metabolism*

Substances

  • Interleukin-4