RRC ID 47719
Author Kanatsu-Shinohara M, Tanaka T, Ogonuki N, Ogura A, Morimoto H, Cheng PF, Eisenman RN, Trumpp A, Shinohara T.
Title Myc/Mycn-mediated glycolysis enhances mouse spermatogonial stem cell self-renewal.
Journal Genes Dev
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.
Volume 30(23)
Pages 2637-2648
Published 2016-12-1
DOI 10.1101/gad.287045.116
PII 30/23/2637
PMID 28007786
PMC PMC5204355
MeSH 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*
IF 9.527
Times Cited 20
DNA material AxCANCre (RDB01748) AxCANLacZ (RDB01749).