Myc/Mycn-mediated glycolysis enhances mouse spermatogonial stem cell self-renewal

Genes Dev. 2016 Dec 1;30(23):2637-2648. doi: 10.1101/gad.287045.116.


Myc plays critical roles in the self-renewal division of various stem cell types. In spermatogonial stem cells (SSCs), Myc controls SSC fate decisions because Myc overexpression induces enhanced self-renewal division, while depletion of Max, a Myc-binding partner, leads to meiotic induction. However, the mechanism by which Myc acts on SSC fate is unclear. Here we demonstrate a critical link between Myc/Mycn gene activity and glycolysis in SSC self-renewal. In SSCs, Myc/Mycn are regulated by Foxo1, whose deficiency impairs SSC self-renewal. Myc/Mycn-deficient SSCs not only undergo limited self-renewal division but also display diminished glycolytic activity. While inhibition of glycolysis decreased SSC activity, chemical stimulation of glycolysis or transfection of active Akt1 or Pdpk1 (phosphoinositide-dependent protein kinase 1 ) augmented self-renewal division, and long-term SSC cultures were derived from a nonpermissive strain that showed limited self-renewal division. These results suggested that Myc-mediated glycolysis is an important factor that increases the frequency of SSC self-renewal division.

Keywords: Myc; glycolysis; self-renewal; spermatogenesis; spermatogonial stem cells.

Publication types

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

MeSH terms

  • 3-Phosphoinositide-Dependent Protein Kinases / metabolism
  • Animals
  • Cell Division / genetics
  • Cell Proliferation / genetics
  • Cell Self Renewal / genetics*
  • Gene Expression Regulation, Developmental / genetics*
  • Gene Knockout Techniques
  • Glycolysis / genetics*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • N-Myc Proto-Oncogene Protein / genetics
  • N-Myc Proto-Oncogene Protein / metabolism*
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • RNA Splicing Factors / metabolism
  • Spermatogonia / cytology*
  • Stem Cells / enzymology
  • Stem Cells / metabolism*


  • MYCN protein, mouse
  • N-Myc Proto-Oncogene Protein
  • Proto-Oncogene Proteins c-myc
  • RNA Splicing Factors
  • Rbfox1 protein, mouse
  • 3-Phosphoinositide-Dependent Protein Kinases
  • Pdpk1 protein, mouse