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Functional Differences between GDNF-Dependent and FGF2-Dependent Mouse Spermatogonial Stem Cell Self-Renewal
Open accessAbstract
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.
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Cites
The dominant-white spotting (W) locus of the mouse encodes the c-kit proto-oncogene
Geissler, E. N., Ryan, M. A., & Housman, D. E. (1988) · Cell · doi:10.1016/0092-8674(88)90020-7 · Cited by 1,287
Goriely, A., McVean, G. A. T., van Pelt, A. M. M., O'Rourke, A. W., Wall, S. A., de Rooij, D. G., & Wilkie, A. O. M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500267102 · Cited by 146
Cited by
The Sertoli cell: one hundred fifty years of beauty and plasticity
França, L. R., Hess, R. A., Dufour, J. M., Hofmann, M. C., & Griswold, M. D. (2016) · Andrology · doi:10.1111/andr.12165 · Cited by 419
The nature and dynamics of spermatogonial stem cells
de Rooij, D. G. (2017) · Development · doi:10.1242/dev.146571 · Cited by 313
Metadata
- Authors
- Takashima, S., Kanatsu-Shinohara, M., Tanaka, T., Morimoto, H., Inoue, K., Ogonuki, N., Jijiwa, M., Takahashi, M., Ogura, A., & Shinohara, T.
- Venue
- Stem Cell Reports
- Publisher
- Elsevier BV
- Published
- 2015-03
- Volume
- 4
- Issue
- 3
- Pages
- 489-502
- ISSN
- 2213-6711 (ISSN-L)
- OpenAlex
- W2044213811
- Cited by
- 185
- References
- 2
- FWCI
- 18.35
- Type
- journal article
- Language
- en
- Open access
- gold
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- The paper
- Takashima, S., Kanatsu-Shinohara, M., Tanaka, T., Morimoto, H., Inoue, K., Ogonuki, N., Jijiwa, M., Takahashi, M., Ogura, A., & Shinohara, T. (2015). Functional Differences between GDNF-Dependent and FGF2-Dependent Mouse Spermatogonial Stem Cell Self-Renewal. Stem Cell Reports. https://doi.org/10.1016/j.stemcr.2015.01.010
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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