The research in Dr. Brinster’s laboratory focuses on the biology of the spermatogonial stem cell (SSC), which is responsible for the continuity of spermatogenesis in the adult male. A spermatogonial transplantation technique has been developed that provides a functional assay of stem cell activity, thereby enabling for the first time an analysis of this unique and valuable stem cell population. Using the transplantation assay the surface antigenic profile of the SSC has been established for several species, and this information allows highly enriched populations of stem cells to be obtained. These enriched SSCs from mouse and rat can now be cultured, and their number increased for long periods. Techniques to extend the culture system to farm animals and primates are under investigation. Additionally, genes are being introduced into the SSC as a technique to modify the germline of animals. Development of culture and gene modification methods for rodent SSCs will lay the foundation for similar approaches in larger animals, particularly farm animals. The culture and enrichment strategies also are being used to study gene activity in stem cells and differentiating daughter cells arising from the stem cells. Using similar methods, signaling pathways active in the fate decision determining stem cell self-renewal or differentiation are under investigation. Since the SSC is the only adult stem cell for which there exists a long-term in vitro culture system and a quantitative functional transplantation assay, it provides a powerful model to understand stem cell function in all adult stem cell systems. In addition, the SSC is the only stem cell in the adult that continually replicates and transmits genes to the next generation. Perhaps most important, it is the vehicle for species continuity and evolutionary adaptation.
Wu X., Goodyear S.M., Abramowitz L.K., Bartolomei M.S., Tobias J.W., Avarbock M.R., Brinster R.L. Fertile offspring derived from mouse spermatogonial stem cells cryopreserved for more than 14 years. Human Reproduction (Oxford, England) 27: 1249-59, 2012.Oatley, J.M. Brinster, R.L. The germline stem cell niche unit in mammalian testes. Physiol. Rev. 92: 577-95, 2012.Niu, Z. Goodyear, S.M. Rao, S. Wu, X. Tobias, J.W. Avarbock, M.R. Brinster, R.L. MicroRNA-21 regulates the self-renewal of mouse spermatogonial stem cells. Proc. Natl. Acad. Sci. USA 108: 12740-5, 2011.Kubota H., Wu X., Goodyear S.M., Avarbock M.R., Brinster R.L. Glial cell line-derived neurotrophic factor and endothelial cells promote self-renewal of rabbit germ cells with spermatogonial stem cell properties. FASEB J. 25: 2604-14, 2011.Ginsberg, J. P., Brinster, R. L. Transplantation of cryopreserved spermatogonia. Principles & Practice of Fertility Preservation Chapter 15, Section IV : 199-208, 2011.Oatley, J. M., Oatley, M. J., Avarbock, M. R., Tobias, J. W., Brinster, R. L. Colony stimulating factor 1 is an extrinsic stimulator of mouse spermatogonial stem cell self-renewal. Development 136: 1191-1199, 2009.Wu, X, Schmidt, J.A., Avarbock, M.R., Tobias, J. W., Carlson, C. A., Kolon, T. F., Ginsberg, J. P., Brinster, R. L. Prepubertal human spermatogonia and mouse gonocytes share conserved gene expression of germline stem cell regulatory molecules. Proc. Natl. Acad. Sci. USA 106: 21672-21677, 2009.Oatley, J. M., Brinster, R. L. Regulation of spermatogonial stem cell self-renewal in mammals. Annu. Rev. Cell Dev. Biol. 24: 263-286, 2008.Brinster, R.L. Male germline stem cells: from mice to men. Science 316: 404-5, 2007.Kubota, H. Avarbock, M.R. Brinster, R.L. Growth factors essential for self-renewal and expansion of mouse spermatogonial stem cells. Proc. Natl. Acad. Sci. USA 101: 16489-94, 2004.Brinster, R.L. Germline stem cell transplantation and transgenesis. Science 296: 2174-6, 2002.