RGD Reference Report - Identification of glial cell line-derived neurotrophic factor-regulated genes important for spermatogonial stem cell self-renewal in the rat. - Rat Genome Database

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

Authors: Schmidt, JA  Avarbock, MR  Tobias, JW  Brinster, RL 
Citation: Schmidt JA, etal., Biol Reprod. 2009 Jul;81(1):56-66. Epub 2009 Apr 1.
RGD ID: 2316287
Pubmed: (View Article at PubMed) PMID:19339709
DOI: Full-text: DOI:10.1095/biolreprod.108.075358

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.



Gene Ontology Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Etv5  (ETS variant transcription factor 5)
Hoxc4  (homeo box C4)

Objects referenced in this article
Strain SD-Tg(hsMt-LacZ)Reh null Rattus norvegicus

Additional Information