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

First Author  Kanatsu-Shinohara M Year  2016
Journal  Genes Dev Volume  30
Issue  23 Pages  2637-2648
PubMed ID  28007786 Mgi Jnum  J:237912
Mgi Id  MGI:5817511 Doi  10.1101/gad.287045.116
Citation  Kanatsu-Shinohara M, et al. (2016) Myc/Mycn-mediated glycolysis enhances mouse spermatogonial stem cell self-renewal. Genes Dev 30(23):2637-2648
abstractText  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.
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