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Title: Myc/Mycn-mediated glycolysis enhances mouse spermatogonial stem cell self-renewal
Authors: Kanatsu-Shinohara, Mito
Tanaka, Takashi
Ogonuki, Narumi
Ogura, Atsuo
Morimoto, Hiroko
Cheng, Pei Feng
Eisenman, Robert N.
Trumpp, Andreas
Shinohara, Takashi
Author's alias: 篠原, 隆司
Keywords: glycolysis
Myc
self-renewal
spermatogenesis
spermatogonial stem cells
Issue Date: 1-Dec-2016
Publisher: Cold Spring Harbor Laboratory
Journal title: Genes & Development
Volume: 30
Issue: 23
Start page: 2637
End page: 2648
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.
Description: Myc/Mycn遺伝子を介した解糖系による精子幹細胞の自己複製の促進 --男性不妊症の治療法開発・新規遺伝子改変動物作成への貢献に期待--. 京都大学プレスリリース. 2016-12-22.
Rights: © 2016 Kanatsu-Shinohara et al.; Published by Cold Spring Harbor Laboratory Press
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
URI: http://hdl.handle.net/2433/230536
DOI(Published Version): 10.1101/gad.287045.116
PubMed ID: 28007786
Related Link: https://www.kyoto-u.ac.jp/ja/research-news/2016-12-22
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