Journal
GENES & DEVELOPMENT
Volume 30, Issue 23, Pages 2637-2648Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.287045.116
Keywords
glycolysis; Myc; self-renewal; spermatogenesis; spermatogonial stem cells
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Funding
- Uehara Memorial Foundation
- Takeda Foundation
- Naito Foundation
- Japan Society for the Promotion of Science (KAKENHI) [JP25112003, JP15H01510]
- Japan Science and Technology Agency (PRESTO)
- National Cancer Institute (National Institutes of Health) [RO1 CA57138]
- Grants-in-Aid for Scientific Research [25112003, 26430100] Funding Source: KAKEN
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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 Foxo 1, 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 Aktl or Pdpkl (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.
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