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

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

Author information

1
Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
2
Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency, Kyoto 606-8501, Japan.
3
Bioresource Center, RIKEN, Tsukuba 305-0074, Japan.
4
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
5
Division of Stem Cells and Cancer, Deutsches Krebsforshungszentrum (DKFZ), 69120 Heidelberg, Germany.

Abstract

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

PMID:
28007786
PMCID:
PMC5204355
DOI:
10.1101/gad.287045.116
[Indexed for MEDLINE]
Free PMC Article

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