Small molecule inhibitors promote efficient generation of induced pluripotent stem cells from human skeletal myoblasts

Stem Cells Dev. 2013 Jan 1;22(1):114-23. doi: 10.1089/scd.2012.0157. Epub 2012 Jul 30.

Abstract

Human somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) by ectopic expression of key transcription factors. iPSCs have been generated from a variety of cell types. However, iPSC induction from human myoblasts has not yet been reported. Human primary skeletal myoblasts can be cultured from diagnostic muscle biopsy specimens, and thousands of lines are frozen and stored in biobanks, and are a valuable source for iPSC-based etiological and pathogenic studies. Our aim was to generate iPSCs from human skeletal myoblasts enriched from muscle biopsy samples. We used retro- or Sendai virus vector-mediated reprogramming of enriched human myoblasts from 7 donors. We show that stable iPSC lines can be generated from human myoblasts at efficiency similar to that of fibroblasts when appropriate media is used, and the efficiency of the feeder-free iPSC generation can be significantly improved by inhibitors of histone deacetylase (sodium butyrate) and TGF-β signaling (SB431542).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Antigens, Differentiation / metabolism
  • Benzamides / pharmacology*
  • Butyric Acid / pharmacology*
  • Cell Culture Techniques
  • Cell Transformation, Neoplastic
  • Cells, Cultured
  • Culture Media
  • Dioxoles / pharmacology*
  • Female
  • Gene Silencing
  • Histone Deacetylase Inhibitors / pharmacology*
  • Humans
  • Induced Pluripotent Stem Cells / drug effects
  • Induced Pluripotent Stem Cells / physiology*
  • Infant
  • Infant, Newborn
  • Male
  • Mice
  • Mice, Nude
  • Middle Aged
  • Muscle, Skeletal / pathology
  • Myoblasts, Skeletal / physiology*
  • Retroviridae / genetics
  • Sendai virus / genetics
  • Signal Transduction / drug effects
  • Teratoma / pathology
  • Transduction, Genetic
  • Transforming Growth Factor beta / physiology
  • Young Adult

Substances

  • 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide
  • Antigens, Differentiation
  • Benzamides
  • Culture Media
  • Dioxoles
  • Histone Deacetylase Inhibitors
  • Transforming Growth Factor beta
  • Butyric Acid