Functional Differences between GDNF-Dependent and FGF2-Dependent Mouse Spermatogonial Stem Cell Self-Renewal

• Takashima, Seiji

• Kanatsu-Shinohara, Mito

• Tanaka, Takashi

• Morimoto, Hiroko

• Inoue, Kimiko

• Ogonuki, Narumi

• Jijiwa, Mayumi

• Takahashi, Masahide

• Ogura, Atsuo

• Shinohara, Takashi

Abstract

Spermatogonial stem cells (SSCs) are required for spermatogenesis. Earlier studies showed that glial cell line-derived neurotrophic factor (GDNF) was indispensable for SSC self-renewal by binding to the GFRA1/RET receptor. Mice with mutations in these molecules showed impaired spermatogenesis, which was attributed to SSC depletion. Here we show that SSCs undergo GDNF-independent self-renewal. A small number of spermatogonia formed colonies when testis fragments from a Ret mutant mouse strain were transplanted into heterologous recipients. Moreover, fibroblast growth factor 2 (FGF2) supplementation enabled in vitro SSC expansion without GDNF. Although GDNF-mediated self-renewal signaling required both AKT and MAP2K1/2, the latter was dispensable in FGF2-mediated self-renewal. FGF2-depleted testes exhibited increased levels of GDNF and were enriched for SSCs, suggesting that the balance between FGF2 and GDNF levels influences SSC self-renewal in vivo. Our results show that SSCs exhibit at least two modes of self-renewal and suggest complexity of SSC regulation in vivo.

Journal

• Stem Cell Reports

  Stem Cell Reports 4 (3), 489-502, 2015-02

  Elsevier Inc.

Details

• CRID: 1050001335802541184
• NII Article ID: 120005540400
• ISSN: 22136711
• HANDLE: 2433/193679
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • CiNii Articles