NANOG Reverses the Myogenic Differentiation Potential of Senescent Stem Cells by Restoring ACTIN Filamentous Organization and SRF-Dependent Gene Expression

Stem Cells. 2017 Jan;35(1):207-221. doi: 10.1002/stem.2452. Epub 2016 Jul 11.


Cellular senescence as a result of organismal aging or progeroid diseases leads to stem cell pool exhaustion hindering tissue regeneration and contributing to the progression of age related disorders. Here we discovered that ectopic expression of the pluripotent factor NANOG in senescent or progeroid myogenic progenitors reversed cellular aging and restored completely the ability to generate contractile force. To elicit its effects, NANOG enabled reactivation of the ROCK and Transforming Growth Factor (TGF)-β pathways-both of which were impaired in senescent cells-leading to ACTIN polymerization, MRTF-A translocation into the nucleus and serum response factor (SRF)-dependent myogenic gene expression. Collectively our data reveal that cellular senescence can be reversed and provide a novel strategy to regain the lost function of aged stem cells without reprogramming to the pluripotent state. Stem Cells 2017;35:207-221.

Keywords: ACTIN polymerization; Aging; Contraction; NANOG; Progeria; SRF; Senescence; Smooth muscle differentiation; Stem cells.

MeSH terms

  • Actins / metabolism*
  • Aged
  • Cell Differentiation* / genetics
  • Cellular Senescence* / genetics
  • Gene Expression Regulation*
  • Genome, Human
  • Humans
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism*
  • Models, Biological
  • Muscle Development / genetics
  • Myofibroblasts / metabolism
  • Nanog Homeobox Protein / metabolism*
  • Phenotype
  • Progeria / genetics
  • Progeria / pathology
  • Serum Response Factor / metabolism*
  • Signal Transduction
  • Trans-Activators / metabolism
  • Transcription, Genetic
  • Transforming Growth Factor beta / metabolism
  • rho-Associated Kinases / metabolism


  • Actins
  • MRTFA protein, human
  • Nanog Homeobox Protein
  • Serum Response Factor
  • Trans-Activators
  • Transforming Growth Factor beta
  • rho-Associated Kinases