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Stem Cell Reports. 2015 Mar 10;4(3):489-502. doi: 10.1016/j.stemcr.2015.01.010. Epub 2015 Feb 12.

Functional differences between GDNF-dependent and FGF2-dependent mouse spermatogonial stem cell self-renewal.

Author information

1
Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
2
Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan; Japan Science and Technology Agency, PRESTO, Kyoto 606-8501, Japan.
3
The Institute for Physical and Chemical Research (RIKEN), Bioresource Center, Tsukuba 305-0074, Japan.
4
Department of Pathology, Graduate School of Medicine, Nagoya University, Nagoya 466-8550, Japan.
5
Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan. Electronic address: tshinoha@virus.kyoto-u.ac.jp.

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.

PMID:
25684228
PMCID:
PMC4375941
DOI:
10.1016/j.stemcr.2015.01.010
[Indexed for MEDLINE]
Free PMC Article

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