Identification of Glial Cell Line-Derived Neurotrophic Factor-Regulated Genes Important for Spermatogonial Stem Cell Self-Renewal in the Rat1
Open Access
- 1 July 2009
- journal article
- Published by Oxford University Press (OUP) in Biology of Reproduction
- Vol. 81 (1), 56-66
- https://doi.org/10.1095/biolreprod.108.075358
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.Keywords
This publication has 39 references indexed in Scilit:
- ETV5 Is Required for Continuous Spermatogenesis in Adult Mice and May Mediate Blood–Testes Barrier Function and Testicular Immune PrivilegeAnnals of the New York Academy of Sciences, 2007
- Analysis of Gene Expression in Bovine Testis Tissue Prior to Ectopic Testis Tissue Xenografting and During the Grafting Period1Biology of Reproduction, 2007
- Identifying genes important for spermatogonial stem cell self-renewal and survivalProceedings of the National Academy of Sciences, 2006
- ERM is required for transcriptional control of the spermatogonial stem cell nicheNature, 2005
- Profiling Gene Expression During the Differentiation and Development of the Murine Embryonic Gonad1Biology of Reproduction, 2005
- Biological Activity of Cryopreserved Bovine Spermatogonial Stem Cells During In Vitro Culture1Biology of Reproduction, 2004
- Culture Conditions and Single Growth Factors Affect Fate Determination of Mouse Spermatogonial Stem Cells1Biology of Reproduction, 2004
- The Murine Testicular Transcriptome: Characterizing Gene Expression in the Testis During the Progression of Spermatogenesis1Biology of Reproduction, 2004
- Defining the spermatogonial stem cellDevelopmental Biology, 2004
- Neurogenin3 delineates the earliest stages of spermatogenesis in the mouse testisDevelopmental Biology, 2004