title: Myc/Mycn-mediated glycolysis enhances mouse spermatogonial stem cell self-renewal.
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.
authors.affiliation: Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.|Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency, Kyoto 606-8501, Japan.
authors.forename: Mito
authors.initials: M
authors.lastname: Kanatsu-Shinohara
authors.affiliation: Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Bioresource Center, RIKEN, Tsukuba 305-0074, Japan.
authors.forename: Narumi
authors.initials: N
authors.lastname: Ogonuki
authors.affiliation: Bioresource Center, RIKEN, Tsukuba 305-0074, Japan.
authors.forename: Atsuo
authors.initials: A
authors.lastname: Ogura
authors.affiliation: Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Morimoto
authors.affiliation: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
authors.forename: Pei Feng
authors.initials: PF
authors.lastname: Cheng
authors.affiliation: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Eisenman
authors.affiliation: Division of Stem Cells and Cancer, Deutsches Krebsforshungszentrum (DKFZ), 69120 Heidelberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Trumpp
authors.affiliation: Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Shinohara
mesh_terms: D064413:3-Phosphoinositide-Dependent Protein Kinases / Q000378:metabolism; D000818:Animals; D002455:Cell Division / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D000066673:Cell Self Renewal / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D055786:Gene Knockout Techniques; D006019:Glycolysis / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000071447:N-Myc Proto-Oncogene Protein / Q000235:genetics / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D000072260:RNA Splicing Factors / Q000378:metabolism; D013093:Spermatogonia / Q000166:cytology*; D013234:Stem Cells / Q000201:enzymology / Q000378:metabolism*
chemical_list: C571825:MYCN protein, mouse; D000071447:N-Myc Proto-Oncogene Protein; D016271:Proto-Oncogene Proteins c-myc; D000072260:RNA Splicing Factors; C465036:Rbfox1 protein, mouse; D064413:3-Phosphoinositide-Dependent Protein Kinases; C578564:Pdpk1 protein, mouse
keywords: Myc; glycolysis; self-renewal; spermatogenesis; spermatogonial stem cells