Register      Login
Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
RESEARCH ARTICLE

Spermatogonial stem cells: unlimited potential

M. Dym A B , Z. He A , J. Jiang A , D. Pant A and M. Kokkinaki A
+ Author Affiliations
- Author Affiliations

A Georgetown University Medical Center, Department of Biochemistry and Molecular and Cellular Biology, 3900 Reservoir Road, NW, Washington, DC 20057, USA.

B Corresponding author. Email: dymm@georgetown.edu

Reproduction, Fertility and Development 21(1) 15-21 https://doi.org/10.1071/RD08221
Published: 9 December 2008

Abstract

Recent reports have demonstrated that adult cells can be reprogrammed to pluripotency, but mostly with genes delivered using retroviruses. Some of the genes are cancer causing; thus, these adult-derived embryonic stem (ES)-like cells cannot be used for therapy to cure human diseases. Remarkably, it has also been demonstrated recently by several groups that, in mice, spermatogonial stem cells (SSCs) can be reprogrammed to ES-like cells without the necessity of exogenously added genes. SSCs constitute one of the most important stem cell systems in the body, not only because they produce spermatozoa that transmit genetic information from generation to generation, but also because of the recent studies showing their remarkable plasticity. Very little is known about SSCs in humans, except for the earlier work of Clermont and colleagues who demonstrated that there are Adark and Apale spermatogonia, with the Adark referred to as the reserve stem cells and the Apale being the renewing stem cells. We now demonstrate that G protein-coupled receptor 125 (GPR125) may be a marker for human SSCs. Putative human SSCs can also be reprogrammed to pluripotency. We were able to achieve this result without the addition of genes, suggesting that human SSCs have considerable potential for cell-based, autologous organ regeneration therapy for various diseases.

Additional keywords: differentiation, embryonic stem cells, GFRA1, GPR125, pluripotency, renewal.


References

Aoi, T. , Yae, K. , Nakagawa, M. , Ichisaka, T. , Okita, K. , Takahashi, K. , Chiba, T. , and Yamanaka, S. (2008). Generation of pluripotent stem cells from adult mouse liver and stomach cells. Science 321, 699–702.
Crossref | GoogleScholarGoogle Scholar | PubMed | CAS | Conrad S., Renninger M., Hennenlotter J., Wiesner T., Just L., et al. (2008). Generation of pluripotent stem cells from adult human testis. Nature, in press. doi:10.1038/NATURE07404

Costoya, J. A. , Hobbs, R. M. , Barna, M. , Cattoretti, G. , Manova, K. , Sukhwani, M. , Orwig, K. E. , Wolgemuth, D. J. , and Pandolfi, P. P. (2004). Essential role of Plzf in maintenance of spermatogonial stem cells. Nat. Genet. 36, 653–659.
Crossref | GoogleScholarGoogle Scholar | PubMed | CAS | Dann C. T., Alvarado A. L., Molyneux L. A., Denard B. S., Garbers D. L., and Porteus M. H. (2008). Spermatogonial stem cell self renewal requires OCT4, a factor down-regulated during retinoic acid induced differentiation. Stem Cells, in press.

de Rooij, D. G. , and Grootegoed, J. A. (1998). Spermatogonial stem cells. Curr. Opin. Cell Biol. 10, 694–701.
Crossref | GoogleScholarGoogle Scholar | PubMed | CAS | Golestaneh N., Kokkinaki M., Jiang J., DeStefano D., Fernandez-Bueno C., Gallicano Y., and Dym M. (2007). Human sperm stem cells can ‘de-differentiate’ into pluripotency. In ‘Proceedings of the American Society of Cell Biology, Annual Meeting’.

Greenbaum, M. P. , Yan, W. , Wu, M. H. , Lin, Y. N. , Agno, J. E. , Sharma, M. , Braun, R. E. , Rajkovic, A. , and Matzuk, M. M. (2006). TEX14 is essential for intercellular bridges and fertility in male mice. Proc. Natl Acad. Sci. USA 103, 4982–4987.
Crossref | GoogleScholarGoogle Scholar | PubMed | CAS | He Z., Jiang J., Hofmann M. C., and Dym M. (2007). Gfra1 silencing in mouse spermatogonial stem cells results in their differentiation via the inactivation of RET tyrosine kinase. Biol. Reprod. 77, 723–733.

Hermann, B. P. , Sukhwani, M. , Lin, C. C. , Sheng, Y. , and Tomko, J. , et al. (2007). Characterization, cryopreservation, and ablation of spermatogonial stem cells in adult rhesus macaques. Stem Cells 25, 2330–2338.
Crossref | GoogleScholarGoogle Scholar | PubMed | CAS | Stadtfeld M., Nagaya M., Utikal J., Weir G., and Hochedlinger K. (2008). Induced pluripotent stem cells generated without viral integration. ScienceXpress, in press.

Takahashi, K. , and Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663–676.
Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |

Takahashi, K. , Tanabe, K. , Ohnuki, M. , Narita, M. , Ichisaka, T. , Tomoda, K. , and Yamanaka, S. (2007). Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131, 861–872.
Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |

Wernig, M. , Meissner, A. , Foreman, R. , Brambrink, T. , Ku, M. , Hochedlinger, K. , Bernstein, B. E. , and Jaenisch, R. (2007). In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature 448, 318–324.
Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |

Yoshida, S. , Nabeshima, Y. , and Nakagawa, T. (2008). Stem cell heterogeneity: actual and potential stem cell compartments in mouse spermatogenesis. Ann. N. Y. Acad. Sci. 1120, 47–58.
Crossref | GoogleScholarGoogle Scholar |

Yoshinaga, K. , Nishikawa, S. , Ogawa, M. , Hayashi, S. , Kunisada, T. , Fujimoto, T. , and Nishikawa, S. (1991). Role of c-kit in mouse spermatogenesis: identification of spermatogonia as a specific site of c-kit expression and function. Development 113, 689–699.
PubMed |  CAS |