Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2093782 | Stem Cell Reports | 2015 | 14 Pages |
•GDNF is dispensable for spermatogonial stem cell (SSC) self-renewal•GFRA1 is expressed in most SSCs•In vivo depletion of FGF2 in the seminiferous tubules enriches SSCs•Self-renewal by GDNF, but not FGF2, requires MAP2K1/2
SummarySpermatogonial 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.
Graphical AbstractFigure optionsDownload full-size imageDownload as PowerPoint slide