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19339709
Identification of glial cell line-derived neurotrophic factor-regulated genes important for spermatogonial stem cell self-renewal in the rat.

Biol Reprod, 2009/7;81(1):56-66.

Schmidt JA[1], Avarbock MR, Tobias JW, Brinster RL

Affiliations

PMID: 19339709DOI: 10.1095/biolreprod.108.075358

Impact factor: 4.161

Abstract
Spermatogonial stem cells (SSCs) provide the foundation for spermatogenesis throughout the life of a male. Because SSCs of many species can colonize the mouse testis, and glial cell line-derived neurotrophic factor (GDNF) is responsible for stimulating SSC self-renewal in rodents, we reasoned that molecular mechanisms of SSC self-renewal are similar across species. GDNF-regulated genes have been identified in mouse SSCs; however, downstream targets of GDNF are unknown in other species. The objective of this work was to identify GDNF-regulated genes in rat SSCs and to define the biological significance of these genes for rat SSC self-renewal. We conducted microarray analysis on cultured rat germ cells enriched for SSCs in the presence and absence of GDNF. Many GDNF-regulated genes were identified, most notably, Bcl6b and Etv5, which are important for mouse SSC self-renewal. Bcl6b was the most highly regulated gene in both the rat and mouse. Additionally, we identified three novel GDNF-regulated genes in rat SSCs: Bhlhe40, Hoxc4, and Tec. Small interfering RNA treatment for Bcl6b, Etv5, Bhlhe40, Hoxc4, and Tec resulted in a decrease in SSC number, as determined by transplantation, without a change in total cell number within the culture. These data indicate that, like in the mouse SSC, Bcl6b and Etv5 are important for rat SSC self-renewal, suggesting that these genes may be important for SSCs in all mammals. Furthermore, identification of three novel GDNF-regulated genes in the rat SSC extends our knowledge of SSC activity and broadens the foundation for understanding this process in higher species, including humans.
MeSH terms
Animals; Antigens, Neoplasm; Cell Adhesion Molecules; Cell Proliferation; Cells, Cultured; Epithelial Cell Adhesion Molecule; Gene Expression Regulation; Glial Cell Line-Derived Neurotrophic Factor; Male; Mice; Mice, Nude; Mice, Transgenic; Rats; Rats, Sprague-Dawley; Rats, Transgenic; Spermatogonia; Stem Cells
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